Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Autophagy in Neurodegenerative Diseases: From Mechanism to Therapeutic Approach

  • Nah, Jihoon (Global Research Laboratory, School of Biological Science, Seoul National University) ;
  • Yuan, Junying (Department of Cell Biology, Harvard Medical School) ;
  • Jung, Yong-Keun (Global Research Laboratory, School of Biological Science, Seoul National University)
  • Received : 2015.02.06
  • Accepted : 2015.02.09
  • Published : 2015.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

Autophagy is a lysosome-dependent intracellular degradation process that allows recycling of cytoplasmic constituents into bioenergetic and biosynthetic materials for maintenance of homeostasis. Since the function of autophagy is particularly important in various stress conditions, perturbation of autophagy can lead to cellular dysfunction and diseases. Accumulation of abnormal protein aggregates, a common cause of neurodegenerative diseases, can be reduced through autophagic degradation. Recent studies have revealed defects in autophagy in most cases of neurodegenerative disorders. Moreover, deregulated excessive autophagy can also cause neurodegeneration. Thus, healthy activation of autophagy is essential for therapeutic approaches in neurodegenerative diseases and many autophagy-regulating compounds are under development for therapeutic purposes. This review describes the overall role of autophagy in neurodegeneration, focusing on various therapeutic strategies for modulating specific stages of autophagy and on the current status of drug development.

Keywords

References

  1. Abrahamsen, H., Stenmark, H., and Platta, H.W. (2012). Ubiquitination and phosphorylation of Beclin 1 and its binding partners: Tuning class III phosphatidylinositol 3-kinase activity and tumor suppression. FEBS Lett. 586, 1584-1591. https://doi.org/10.1016/j.febslet.2012.04.046
  2. Alcalay, R.N., Caccappolo, E., Mejia-Santana, H., Tang, M.X., Rosado, L., Ross, B.M., Verbitsky, M., Kisselev, S., Louis, E.D., Comella, C., et al. (2010). Frequency of known mutations in early- onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study. Arch. Neurol. 67, 1116-1122.
  3. Alegre-Abarrategui, J., Christian, H., Lufino, M.M., Mutihac, R., Venda, L.L., Ansorge, O., and Wade-Martins, R. (2009). LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum. Mol. Genet. 18, 4022-4034. https://doi.org/10.1093/hmg/ddp346
  4. Andersen, P.M., and Al-Chalabi, A. (2011). Clinical genetics of amyotrophic lateral sclerosis: what do we really know? Nat. Rev. Neurol. 7, 603-615. https://doi.org/10.1038/nrneurol.2011.150
  5. Anglade, P., Vyas, S., Javoy-Agid, F., Herrero, M.T., Michel, P.P., Marquez, J., Mouatt-Prigent, A., Ruberg, M., Hirsch, E.C., and Agid, Y. (1997). Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol. Histopathol. 12, 25-31.
  6. Barmada, S.J., Serio, A., Arjun, A., Bilican, B., Daub, A., Ando, D.M., Tsvetkov, A., Pleiss, M., Li, X., Peisach, D., et al. (2014). Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat. Chem. Biol. 10, 677-685. https://doi.org/10.1038/nchembio.1563
  7. Bonifati, V. (2006). Parkinson's disease: the LRRK2-G2019S mutation: opening a novel era in Parkinson's disease genetics. Eur. J. Hum. Genet. 14, 1061-1062. https://doi.org/10.1038/sj.ejhg.5201695
  8. Boya, P., Reggiori, F., and Codogno, P. (2013). Emerging regulation and functions of autophagy. Nat. Cell Biol. 15, 713-720. https://doi.org/10.1038/ncb2788
  9. Burli, R.W., Luckhurst, C.A., Aziz, O., Matthews, K.L., Yates, D., Lyons, K.A., Beconi, M., McAllister, G., Breccia, P., Stott, A.J., et al. (2013). Design, synthesis, and biological evaluation of potent and selective class IIa histone deacetylase (HDAC) inhibitors as a potential therapy for Huntington's disease. J. Med. Chem. 56, 9934-9954. https://doi.org/10.1021/jm4011884
  10. Caccamo, A., Majumder, S., Richardson, A., Strong, R., and Oddo, S. (2010). Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J. Biol. Chem. 285, 13107-13120. https://doi.org/10.1074/jbc.M110.100420
  11. Chen, D., Fan, W., Lu, Y., Ding, X., Chen, S., and Zhong, Q. (2012). A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate. Mol. Cell. 45, 629-641. https://doi.org/10.1016/j.molcel.2011.12.036
  12. Cherra, S.J. 3rd, and Chu, C.T. (2008). Autophagy in neuroprotection and neurodegeneration: A question of balance. Future Neurol. 3, 309-323.
  13. Ching, J.K., and Weihl, C.C. (2013). Rapamycin-induced autophagy aggravates pathology and weakness in a mouse model of VCPassociated myopathy. Autophagy 9, 799-800. https://doi.org/10.4161/auto.23958
  14. Cortes, C.J, and La Spada, A.R. (2014). The many faces of autophagy dysfunction in Huntington's disease: from mechanism to therapy. Drug Discov. Today 19, 963-971. https://doi.org/10.1016/j.drudis.2014.02.014
  15. Coune, P.G., Bensadoun, J.C., Aebischer, P., and Schneider, B.L. (2011). Rab1A over-expression prevents Golgi apparatus fragmentation and partially corrects motor deficits in an alphasynuclein based rat model of Parkinson's disease. J. Parkinsons Dis. 1, 373-387.
  16. Crippa, V., Sau, D., Rusmini, P., Boncoraglio, A., Onesto, E., Bolzoni, E., Galbiati, M., Fontana ,E., Marino, M., Carra, S., et al. (2010). The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum. Mol. Genet. 19, 3440-3456. https://doi.org/10.1093/hmg/ddq257
  17. Decressac, M., Mattsson, B., Weikop, P., Lundblad, M., Jakobsson, J., and Bjorklund, A. (2013). TFEB-mediated autophagy rescues midbrain dopamine neurons from $\alpha$-synuclein toxicity. Proc. Natl. Acad. Sci. USA 110, E1817-1826. https://doi.org/10.1073/pnas.1305623110
  18. Deng, Y.N., Shi, J., Liu, J., and Qu, Q.M. (2013). Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy. Neurochem. Int. 63, 1-9. https://doi.org/10.1016/j.neuint.2013.04.005
  19. Dolan, P.J., and Johnson, G.V. (2010). A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. J. Biol. Chem. 285, 21978-21987. https://doi.org/10.1074/jbc.M110.110940
  20. Du, G., Liu, X., Chen, X., Song, M., Yan, Y., Jiao, R., and Wang, C.C. (2010). Drosophila histone deacetylase 6 protects dopaminergic neurons against {alpha}-synuclein toxicity by promoting inclusion formation. Mol. Biol. Cell 21, 2128-2137. https://doi.org/10.1091/mbc.E10-03-0200
  21. Duyao, M.P., Auerbach, A.B., Ryan, A., Persichetti, F., Barnes, G.T., McNeil, S.M., Ge, P., Vonsattel, J.P., Gusella, J.F., Joyner, A.L., et al. (1995). Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 269, 407-410. https://doi.org/10.1126/science.7618107
  22. Ebrahimi-Fakhari, D., Cantuti-Castelvetri, I., Fan, Z., Rockenstein, E., Masliah, E., Hyman, B.T., McLean, P.J., and Unni, V.K. (2011). Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of $\alpha$- synuclein. J. Neurosci. 31, 14508-14520. https://doi.org/10.1523/JNEUROSCI.1560-11.2011
  23. Filimonenko, M., Isakson, P., Finley, K.D., Anderson, M., Jeong, H., Melia, T.J., Bartlett, B.J., Myers, K.M., Birkeland, H.C., Lamark, T. et al. (2010). The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol. Cell 38, 265-279. https://doi.org/10.1016/j.molcel.2010.04.007
  24. Filomeni, G., Graziani, I., De Zio, D., Dini, L., Centonze, D., Rotilio, G., and Ciriolo, M.R. (2012). Neuroprotection of kaempferol by autophagy in models of rotenone-mediated acute toxicity: possible implications for Parkinson's disease. Neurobiol. Aging 33, 767-785. https://doi.org/10.1016/j.neurobiolaging.2010.05.021
  25. Forlenza, O.V., de Paula, V.J., Machado-Vieira, R., Diniz, B.S., and Gattaz, W.F. (2012). Does lithium prevent Alzheimer's disease? Drugs Aging 29, 335-342. https://doi.org/10.2165/11599180-000000000-00000
  26. Fornai, F., Longone, P., Cafaro, L., Kastsiuchenka, O., Ferrucci, M., Manca, M.L., Lazzeri, G., Spalloni, A., Bellio, N., Lenzi, P., et al. (2008). Lithium delays progression of amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 105, 2052-2057. https://doi.org/10.1073/pnas.0708022105
  27. Gamblin, T.C., Chen, F., Zambrano, A., Abraha, A., Lagalwar, S., Guillozet, A.L., Lu, M., Fu, Y., Garcia-Sierra, F., LaPointe, N., et al. (2003). Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 100, 10032-10037. https://doi.org/10.1073/pnas.1630428100
  28. Giordano, S., Darley-Usmar, V., and Zhang, J. (2014). Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease. Redox Biol. 2, 82-90. https://doi.org/10.1016/j.redox.2013.12.013
  29. Hadano, S., Otomo, A., Kunita, R., Suzuki-Utsunomiya, K., Akatsuka, A., Koike, M., Aoki, M., Uchiyama, Y., Itoyama, Y., and Ikeda, J.E. (2010). Loss of ALS2/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking. PLoS One 5, e9805. https://doi.org/10.1371/journal.pone.0009805
  30. Hamano, T., Gendron, T.F., Causevic, E., Yen, S.H., Lin, W.L., Isidoro, C., Deture, M., and Ko, L.W. (2008). Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression. Eur. J. Neurosci. 27, 1119-1130. https://doi.org/10.1111/j.1460-9568.2008.06084.x
  31. Han, H., Wei, W., Duan, W., Guo, Y., Li, Y., Wang, J., Bi, Y., and Li, C. (2014). Autophagy-linked FYVE protein (Alfy) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). In Vitro Cell. Dev. Biol. Anim. [Epub ahead of print]
  32. Hetz, C., Thielen, P., Matus, S., Nassif, M., Court, F., Kiffin, R., Martinez, G., Cuervo, A.M., Brown, R.H., and Glimcher, L.H. (2009). XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 23, 2294-2306. https://doi.org/10.1101/gad.1830709
  33. Hyttinen, J.M., Niittykoski, M., Salminen, A., and Kaarniranta, K. (2013). Maturation of autophagosomes and endosomes: a key role for Rab7. Biochim. Biophys. Acta 1833, 503-510. https://doi.org/10.1016/j.bbamcr.2012.11.018
  34. Jaeger, P.A., Pickford, F., Sun, C.H., Lucin, K.M., Masliah, E., and Wyss-Coray, T. (2010). Regulation of amyloid precursor protein processing by the Beclin 1 complex. PLoS One 5, e11102. https://doi.org/10.1371/journal.pone.0011102
  35. Jia, H., Kast, R.J., Steffan, J.S., and Thomas, E.A. (2012). Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in Huntington's disease mice: implications for the ubiquitinproteasomal and autophagy systems. Hum. Mol. Genet. 21, 5280-5293. https://doi.org/10.1093/hmg/dds379
  36. Jiang, T.F., Zhang, Y.J., Zhou, H.Y., Wang, H.M., Tian, L.P., Liu, J., Ding, J.Q., and Chen, S.D. (2013). Curcumin ameliorates the neurodegenerative pathology in A53T $\alpha$-synuclein cell model of Parkinson's disease through the downregulation of mTOR/ p70S6K signaling and the recovery of macroautophagy. J. Neuroimmune Pharmacol. 8, 356-669. https://doi.org/10.1007/s11481-012-9431-7
  37. Juenemann, K., Schipper-Krom, S., Wiemhoefer, A., Kloss, A., Sanz Sanz, A., and Reits, E.A. (2013). Expanded polyglutaminecontaining N-terminal huntingtin fragments are entirely degraded by mammalian proteasomes. J. Biol. Chem. 288, 27068-27084. https://doi.org/10.1074/jbc.M113.486076
  38. Kaushik, S., and Cuervo, A.M. (2012). Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 22, 407-417. https://doi.org/10.1016/j.tcb.2012.05.006
  39. Kesidou, E., Lagoudaki, R., Touloumi, O., Poulatsidou, K.N., and Simeonidou, C. (2013). Autophagy and neurodegenerative disorders. Neural Regen. Res. 8, 2275-2283.
  40. Kickstein, E., Krauss, S., Thornhill, P., Rutschow, D., Zeller, R., Sharkey, J., Williamson, R., Fuchs, M., Köhler, A., Glossmann, H., et al. (2010). Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc. Natl. Acad. Sci. USA 107, 21830-21835. https://doi.org/10.1073/pnas.0912793107
  41. Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A., Hardiman, O., Burrell, J.R., and Zoing, M.C. (2011). Amyotrophic lateral sclerosis. Lancet 377, 942-955. https://doi.org/10.1016/S0140-6736(10)61156-7
  42. Koga, H., Martinez-Vicente, M., Arias, E., Kaushik, S., Sulzer, D., and Cuervo, A.M. (2011). Constitutive upregulation of chaperone- mediated autophagy in Huntington's disease. J. Neurosci. 31, 18492-18505. https://doi.org/10.1523/JNEUROSCI.3219-11.2011
  43. Komatsu, M., and Ichimura, Y. (2010). Selective autophagy regulates various cellular functions. Genes Cells 15, 923-933. https://doi.org/10.1111/j.1365-2443.2010.01433.x
  44. Lee, J.A. (2012). Neuronal autophagy: a housekeeper or a fighter in neuronal cell survival? Exp. Neurobiol. 21, 1-8. https://doi.org/10.5607/en.2012.21.1.1
  45. Lee, J.H., Yu, W.H., Kumar, A., Lee, S., Mohan, P.S., Peterhoff, C.M., Wolfe, D.M., Martinez-Vicente, M., Massey, A.C., Sovak, G., et al. (2010). Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141, 1146-1158. https://doi.org/10.1016/j.cell.2010.05.008
  46. Li, L., Zhang, X., and Le, W. (2008). Altered macroautophagy in the spinal cord of SOD1 mutant mice. Autophagy 4, 290-293. https://doi.org/10.4161/auto.5524
  47. Li, W.W., Li, J., and Bao, J.K. (2012). Microautophagy: lesserknown self-eating. Cell. Mol. Life Sci. 69, 1125-1136. https://doi.org/10.1007/s00018-011-0865-5
  48. Lin, T.K., Chen, S.D., Chuang, Y.C., Lin, H.Y., Huang, C.R., Chuang, J.H., Wang, P.W., Huang, S.T., Tiao, M.M., Chen, J.B., et al. (2014). Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy. Int. J. Mol. Sci. 15, 1625-1646. https://doi.org/10.3390/ijms15011625
  49. Liu, D., Pitta, M., Jiang, H., Lee, J.H., Zhang, G., Chen, X., Kawamoto, E.M., and Mattson, M.P. (2013). Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol. Aging 34, 1564-1580. https://doi.org/10.1016/j.neurobiolaging.2012.11.020
  50. Lucin, K.M., O'Brien, C.E., Bieri, G., Czirr, E., Mosher, .KI., Abbey, R.J., Mastroeni, D.F., Rogers, J., Spencer, B., Masliah, E., et al. (2013). Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer's disease. Neuron 79, 873-886. https://doi.org/10.1016/j.neuron.2013.06.046
  51. Manzoni, C., Mamais, A., Dihanich, S., Abeti, R., Soutar, M.P., Plun- Favreau, H., Giunti, P., Tooze, S.A., Bandopadhyay, R., and Lewis, P.A. (2013). Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim. Biophys. Acta 1833, 2900-2910. https://doi.org/10.1016/j.bbamcr.2013.07.020
  52. Martin, D.D., Ladha, S., Ehrnhoefer, D.E., and Hayden, M.R. (2015). Autophagy in Huntington disease and huntingtin in autophagy. Trends Neurosci. 38, 26-35. https://doi.org/10.1016/j.tins.2014.09.003
  53. Martinez-Vicente, M., Talloczy, Z., Kaushik, S., Massey, A.C., Mazzulli, J., Mosharov, E.V., Hodara, R., Fredenburg R., Wu, D.C., Follenzi, A., et al. (2008). Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J. Clin. Invest. 118, 777-788.
  54. Martinez-Vicente, M., Talloczy, Z., Wong, E., Tang, G., Koga, H., Kaushik, S., de Vries, R., Arias, E., Harris, S., Sulzer, D., et al. (2010). Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat. Neurosci. 13, 567-576. https://doi.org/10.1038/nn.2528
  55. Millecamps, S., and Julien, J.P. (2013). Axonal transport deficits and neurodegenerative diseases. Nat. Rev. Neurosci. 14, 161-176. https://doi.org/10.1038/nrn3380
  56. Mizushima, N., Yoshimori, T., and Ohsumi, Y. (2011). The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27, 107-132. https://doi.org/10.1146/annurev-cellbio-092910-154005
  57. Mizushima, N. (2010). The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 22, 132-139. https://doi.org/10.1016/j.ceb.2009.12.004
  58. Morimoto, N., Nagai, M., Ohta, Y., Miyazaki, K., Kurata, T., Morimoto, M., Murakami, T., Takehisa, Y., Ikeda, Y., Kamiya, T., et al. (2007). Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res. 1167, 112-117. https://doi.org/10.1016/j.brainres.2007.06.045
  59. Nagata, E., Sawa, A., Ross, C.A., and Snyder, SH. (2004). Autophagosome-like vacuole formation in Huntington's disease lymphoblasts. Neuroreport 15, 1325-1328. https://doi.org/10.1097/01.wnr.0000127073.66692.8f
  60. Nah, J., Pyo, J.O., Jung, S., Yoo, S.M., Kam, T.I., Chang, J., Han, J., Soo A An, S., Onodera, T., and Jung, Y.K. (2013). BECN1/Beclin 1 is recruited into lipid rafts by prion to activate autophagy in response to amyloid $\beta$ 42. Autophagy 9, 2009-2021. https://doi.org/10.4161/auto.26118
  61. Nair, U., Jotwani, A., Geng, J., Gammoh, N., Richerson, D., Yen, W.L., Griffith, J., Nag, S., Wang, K., Moss, T., et al. (2011). SNARE proteins are required for macroautophagy. Cell 146, 290-302. https://doi.org/10.1016/j.cell.2011.06.022
  62. Nakatogawa, H., Suzuki, K., Kamada, Y., and Ohsumi, Y. (2009). Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 10, 458-467. https://doi.org/10.1038/nrm2708
  63. Narendra, D., Tanaka, A., Suen, D.F., and Youle, R.J. (2008). Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183, 795-803. https://doi.org/10.1083/jcb.200809125
  64. Nassif, M., Valenzuela, V., Rojas-Rivera, D., Vidal, R., Matus, S., Castillo, K., Fuentealba, Y., Kroemer, G., Levine, B., and Hetz, C. (2014). Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy 10, 1256-1271. https://doi.org/10.4161/auto.28784
  65. Nixon, R.A., Wegiel, J., Kumar, A., Yu, W.H., Peterhoff, C., Cataldo, A., and Cuervo, A.M. (2005). Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol. 64, 113-122. https://doi.org/10.1093/jnen/64.2.113
  66. Orenstein, S.J., Kuo, S.H., Tasset, I., Arias, E., Koga, H., Fernandez- Carasa, I., Cortes, E., Honig, L.S., Dauer, W., Consiglio, A., et al. (2013). Interplay of LRRK2 with chaperone-mediated autophagy. Nat. Neurosci. 16, 394-406. https://doi.org/10.1038/nn.3350
  67. Pan, P.Y., and Yue, Z. (2014). Genetic causes of Parkinson's disease and their links to autophagy regulation. Parkinsonism Relat. Disord. 20 Suppl 1, S154-157. https://doi.org/10.1016/S1353-8020(13)70037-3
  68. Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., et al. (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859-863.
  69. Pickford, F., Masliah, E., Britschgi, M., Lucin, K., Narasimhan, R., Jaeger, P.A., Small, S., Spencer, B., Rockenstein, E., Levine, B., et al. (2008). The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Invest. 118, 2190-2199.
  70. Pizzasegola, C., Caron, I., Daleno, C., Ronchi, A., Minoia, C., Carrì, M.T., and Bendotti, C. (2009). Treatment with lithium carbonate does not improve disease progression in two different strains of SOD1 mutant mice. Amyotroph. Lateral Scler. 10, 221-228. https://doi.org/10.1080/17482960902803440
  71. Qi, L., and Zhang, X.D. (2014). Role of chaperone-mediated autophagy in degrading Huntington's disease-associated huntingtin protein. Acta Biochim. Biophys. Sin. (Shanghai) 46, 83-91. https://doi.org/10.1093/abbs/gmt133
  72. Querfurth, H.W., and LaFerla, F.M. (2010). Alzheimer's disease. N. Engl. J. Med. 362, 329-344. https://doi.org/10.1056/NEJMra0909142
  73. Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., Scaravilli, F., Easton, D.F., Duden, R., O'Kane, C.J., et al. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585-595. https://doi.org/10.1038/ng1362
  74. Rodriguez-Martín, T., Cuchillo-Ibanez, I., Noble, W., Nyenya, F., Anderton, B.H., and Hanger, D.P. (2013). Tau phosphorylation affects its axonal transport and degradation. Neurobiol. Aging 34, 2146-2157. https://doi.org/10.1016/j.neurobiolaging.2013.03.015
  75. Rohn, T.T., Wirawan, E., Brown, R.J., Harris, J.R., Masliah, E., and Vandenabeele, P. (2011). Depletion of Beclin-1 due to proteolytic cleavage by caspases in the Alzheimer's disease brain. Neurobiol. Dis. 43, 68-78. https://doi.org/10.1016/j.nbd.2010.11.003
  76. Rose, C., Menzies, F.M., Renna, M., Acevedo-Arozena, A., Corrochano, S., Sadiq, O., Brown, S.D., and Rubinsztein, D.C. (2010). Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease. Hum. Mol. Genet. 19, 2144-2153. https://doi.org/10.1093/hmg/ddq093
  77. Russell, R.C., Tian, Y., Yuan, H., Park, H.W., Chang, Y.Y., Kim, J., Kim, H., Neufeld, T.P., Dillin, A., and Guan, K.L. (2013). ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat. Cell Biol. 15, 741-750. https://doi.org/10.1038/ncb2757
  78. Sala, G., Stefanoni, G., Arosio, A., Riva, C., Melchionda, L., Saracchi, E., Fermi, S., Brighina, L., and Ferrarese, C. (2014). Reduced expression of the chaperone-mediated autophagy carrier hsc70 protein in lymphomonocytes of patients with Parkinson's disease. Brain Res. 1546, 46-52. https://doi.org/10.1016/j.brainres.2013.12.017
  79. Sasaki, S. (2011). Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 70, 349-359. https://doi.org/10.1097/NEN.0b013e3182160690
  80. Scarffe, L.A., Stevens, D.A., Dawson, V.L., and Dawson, T.M. (2014). Parkin and PINK1: much more than mitophagy. Trends Neurosci. 37, 315-324. https://doi.org/10.1016/j.tins.2014.03.004
  81. Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B., and Yuan, J. (2006). Regulation of intracellular accumulation of mutant Huntingtin by Beclin1. J. Biol. Chem. 281, 14474-14485. https://doi.org/10.1074/jbc.M600364200
  82. Shibutani, S.T., and Yoshimori, T. (2014) A current perspective of autophagosome biogenesis. Cell Res. 24, 58-68. https://doi.org/10.1038/cr.2013.159
  83. Shintani, T., and Klionsky, D.J. (2004). utophagy in health and disease: a double-edged sword. Science 306, 990-995. https://doi.org/10.1126/science.1099993
  84. Shoji-Kawata, S., Sumpter, R., Leveno, M., Campbell, G.R., Zou, Z., Kinch, L., Wilkins, A.D., Sun, Q., Pallauf, K., MacDuff, D., et al. (2013). Identification of a candidate therapeutic autophagyinducing peptide. Nature 494, 201-206. https://doi.org/10.1038/nature11866
  85. Shpilka, T., Mizushima, N., and Elazar, Z. (2012). Ubiquitin-like proteins and autophagy at a glance. J. Cell Sci. 125, 2343-2348. https://doi.org/10.1242/jcs.093757
  86. Son, S.M., Jung, E.S., Shin, H.J., Byun, J., and Mook-Jung, I. (2012). $A{\beta}$-induced formation of autophagosomes is mediated by RAGE-$CaMKK{\beta}$-AMPK signaling. Neurobiol. Aging 33, 1006.e11-23.
  87. Song, C.Y., Guo, J.F., Liu, Y., and Tang, B.S. (2012). Autophagy and Its Comprehensive Impact on ALS. Int. J. Neurosci. 122, 695-703. https://doi.org/10.3109/00207454.2012.714430
  88. Spencer, B., Potkar, R., Trejo, M., Rockenstein, E., Patrick, C., Gindi, R., Adame, A., Wyss-Coray, T., and Masliah, E. (2009). Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases. J. Neurosci. 29, 13578-13588. https://doi.org/10.1523/JNEUROSCI.4390-09.2009
  89. Staats, K.A., Hernandez, S., Schönefeldt, S., Bento-Abreu, A., Dooley, J., Van Damme P., Liston, A., Robberecht, W., and Van Den Bosch, L. (2013). Rapamycin increases survival in ALS mice lacking mature lymphocytes. Mol. Neurodegener 8, 31. https://doi.org/10.1186/1750-1326-8-31
  90. Steele, J.W., and Gandy, S. (2013). Latrepirdine (Dimebon$^{(R)}$), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy 9, 617-618. https://doi.org/10.4161/auto.23487
  91. Surendran, S., and Rajasankar, S. (2010). Parkinson's disease: oxidative stress and therapeutic approaches. Neurol. Sci. 31, 531-540. https://doi.org/10.1007/s10072-010-0245-1
  92. Tan, C.C., Yu, J.T., Tan, M.S., Jiang, T., Zhu, X.C., and Tan, L. (2014). Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiol. Aging 35, 941-957. https://doi.org/10.1016/j.neurobiolaging.2013.11.019
  93. Tanaka, M., Machida, Y., Niu, S., Ikeda, T., Jana, N.R., Doi, H., Kurosawa, M., Nekooki, M., and Nukina, N. (2004). Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat. Med. 10, 148-154. https://doi.org/10.1038/nm985
  94. Thompson, L,M., Aiken, C,T., Kaltenbach, L.S., Agrawal, N., Illes, K., Khoshnan, A., Martinez-Vincente, M., Arrasate, M., O'Rourke, J.G., Khashwji, H., et al. (2009). IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J. Cell Biol. 187, 1083-1099. https://doi.org/10.1083/jcb.200909067
  95. Tian, Y., Bustos, V., Flajolet, M., and Greengard, P. (2011). A smallmolecule enhancer of autophagy decreases levels of Abeta and APP-CTF via Atg5-dependent autophagy pathway. FASEB J. 25, 1934-1942. https://doi.org/10.1096/fj.10-175158
  96. Tsvetkov, A.S., Miller, J., Arrasate, M., Wong, J.S., Pleiss, M.A., and Finkbeiner, S. (2010). A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc. Natl. Acad. Sci. USA. 107, 16982-16987. https://doi.org/10.1073/pnas.1004498107
  97. Ulamek-Kozio, M., Furmaga-Jablonska, W., Januszewski, S., Brzozowska, J., Scislewska, M., Jablonski, M., and Pluta, R. (2013). Neuronal autophagy: self-eating or self-cannibalism in Alzheimer's disease. Neurochem. Res. 38, 1769-1773. https://doi.org/10.1007/s11064-013-1082-4
  98. Vingtdeux, V., Giliberto, L., Zhao, H., Chandakkar, P., Wu, Q., Simon, J.E., Janle, E.M., Lobo, J., Ferruzzi. M.G., Davies. P., et al. (2010). AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J. Biol. Chem. 285, 9100-9113. https://doi.org/10.1074/jbc.M109.060061
  99. Wacker, J.L., Zareie, M.H., Fong, H., Sarikaya, M., and Muchowski, P.J. (2004). Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat. Struct. Mol. Biol. 11, 1215-1222. https://doi.org/10.1038/nsmb860
  100. Waldemar, G., Dubois, B., Emre, M., Georges, J., McKeith, I.G., Rossor, M., Scheltens, P., Tariska, P., and Winblad, B. (2007). Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline. Eur. J. Neurol. 14, e1-26.
  101. Wang, J.Z., Xia, Y.Y., Grundke-Iqbal, I., and Iqbal, K. (2013). Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J. Alzheimers Dis. 33 Suppl 1, S123-139.
  102. Weidberg, H., Shvets, E., and Elazar, Z. (2011). Biogenesis and cargo selectivity of autophagosomes. Annu. Rev. Biochem. 80, 125-156. https://doi.org/10.1146/annurev-biochem-052709-094552
  103. Yu, W.H., Cuervo, A.M., Kumar, A., Peterhoff, C.M., Schmidt, S.D., Lee, J.H., Mohan, P.S., Mercken, M., Farmery, M.R., Tjernberg, L.O., et al. (2005). Macroautophagy--a novel Beta-amyloid peptide- generating pathway activated in Alzheimer's disease. J. Cell Biol. 171, 87-98. https://doi.org/10.1083/jcb.200505082
  104. Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Zhang, X., Wang, Z., and Le, W. (2011). Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy 7, 412-425. https://doi.org/10.4161/auto.7.4.14541
  105. Zhang ,X., Chen, S., Song, L., Tang, Y., Shen, Y., Jia, L., and Le, W. (2014). MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy 10, 588-602. https://doi.org/10.4161/auto.27710

Cited by

  1. Mitochondrial Quality Control and Disease: Insights into Ischemia-Reperfusion Injury 2017, https://doi.org/10.1007/s12035-017-0503-9
  2. Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand vol.10, 2017, https://doi.org/10.3389/fnmol.2017.00263
  3. The mammalian target of rapamycin at the crossroad between cognitive aging and Alzheimer’s disease vol.1, pp.1, 2015, https://doi.org/10.1038/npjamd.2015.8
  4. Breast cancer cell line MDA-MB-231 miRNA profile expression after BIK interference: BIK involvement in autophagy vol.37, pp.5, 2016, https://doi.org/10.1007/s13277-015-4494-8
  5. Autophagy in Neurodegenerative Diseases and Metal Neurotoxicity vol.41, pp.1-2, 2016, https://doi.org/10.1007/s11064-016-1844-x
  6. Gain-of-function profilin 1 mutations linked to familial amyotrophic lateral sclerosis cause seed-dependent intracellular TDP-43 aggregation vol.25, pp.7, 2016, https://doi.org/10.1093/hmg/ddw024
  7. Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro vol.129, pp.1, 2016, https://doi.org/10.1007/s11060-016-2149-2
  8. Chronic Hypoxia-Induced Autophagy Aggravates the Neuropathology of Alzheimer’s Disease through AMPK-mTOR Signaling in the APPSwe/PS1dE9 Mouse Model vol.48, pp.4, 2015, https://doi.org/10.3233/JAD-150303
  9. Malathion increases apoptotic cell death by inducing lysosomal membrane permeabilization in N2a neuroblastoma cells: a model for neurodegeneration in Alzheimer’s disease vol.3, 2017, https://doi.org/10.1038/cddiscovery.2017.7
  10. Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury vol.5, pp.1, 2015, https://doi.org/10.1038/srep17130
  11. Proteostasis and Diseases of the Motor Unit vol.9, 2016, https://doi.org/10.3389/fnmol.2016.00164
  12. Mitophagy in neurodegenerative diseases 2017, https://doi.org/10.1016/j.neuint.2017.08.004
  13. Low Shear Stress Inhibited Endothelial Cell Autophagy Through TET2 Downregulation vol.44, pp.7, 2016, https://doi.org/10.1007/s10439-015-1491-4
  14. Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice vol.1646, 2016, https://doi.org/10.1016/j.brainres.2016.06.020
  15. Therapeutic Targeting of Autophagy vol.14, 2016, https://doi.org/10.1016/j.ebiom.2016.10.034
  16. Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK vol.13, pp.8, 2017, https://doi.org/10.1080/15548627.2017.1329081
  17. Actions of the antihistaminergic clemastine on presymptomatic SOD1-G93A mice ameliorate ALS disease progression vol.13, pp.1, 2016, https://doi.org/10.1186/s12974-016-0658-8
  18. The double faced role of copper in Aβ homeostasis: A survey on the interrelationship between metal dyshomeostasis, UPS functioning and autophagy in neurodegeneration vol.347, 2017, https://doi.org/10.1016/j.ccr.2017.06.004
  19. Autophagy-Related Deubiquitinating Enzymes Involved in Health and Disease vol.4, pp.4, 2015, https://doi.org/10.3390/cells4040596
  20. Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms vol.8, 2017, https://doi.org/10.3389/fphar.2017.00351
  21. Comparative Microarray Analysis Identifies Commonalities in Neuronal Injury: Evidence for Oxidative Stress, Dysfunction of Calcium Signalling, and Inhibition of Autophagy–Lysosomal Pathway vol.41, pp.3, 2016, https://doi.org/10.1007/s11064-015-1666-2
  22. Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy vol.54, pp.7, 2017, https://doi.org/10.1007/s12035-016-0079-9
  23. Neuronal response in Alzheimer’s and Parkinson’s disease: the effect of toxic proteins on intracellular pathways vol.16, pp.1, 2015, https://doi.org/10.1186/s12868-015-0211-1
  24. Autophagy, its mechanisms and regulation: Implications in neurodegenerative diseases 2017, https://doi.org/10.1016/j.arr.2017.09.005
  25. Selenomethionine Attenuates the Amyloid-β Level by Both Inhibiting Amyloid-β Production and Modulating Autophagy in Neuron-2a/AβPPswe Cells vol.59, pp.2, 2017, https://doi.org/10.3233/JAD-170216
  26. Autophagy Is Involved in the Sevoflurane Anesthesia-Induced Cognitive Dysfunction of Aged Rats vol.11, pp.4, 2016, https://doi.org/10.1371/journal.pone.0153505
  27. Developmental aspects of senescence vol.48, pp.2, 2017, https://doi.org/10.1134/S1062360417020035
  28. Autophagy in neuroinflammatory diseases vol.16, pp.8, 2017, https://doi.org/10.1016/j.autrev.2017.05.015
  29. Cellular mechanisms of peroxynitrite-induced neuronal death vol.133, 2017, https://doi.org/10.1016/j.brainresbull.2017.05.008
  30. Autophagy in Plants – What's New on the Menu? vol.21, pp.2, 2016, https://doi.org/10.1016/j.tplants.2015.10.008
  31. Dysfunction of autophagy as the pathological mechanism of motor neuron disease based on a patient-specific disease model vol.31, pp.4, 2015, https://doi.org/10.1007/s12264-015-1541-9
  32. Augmenting autophagy for prognosis based intervention of COPD-pathophysiology vol.18, pp.1, 2017, https://doi.org/10.1186/s12931-017-0560-7
  33. Resveratrol as a Natural Autophagy Regulator for Prevention and Treatment of Alzheimer’s Disease vol.9, pp.9, 2017, https://doi.org/10.3390/nu9090927
  34. Electroacupuncture protects against ischemic stroke by reducing autophagosome formation and inhibiting autophagy through the mTORC1-ULK1 complex-Beclin1 pathway vol.37, pp.2, 2016, https://doi.org/10.3892/ijmm.2015.2425
  35. Silica nanoparticles induce alpha-synuclein induction and aggregation in PC12-cells vol.258, 2016, https://doi.org/10.1016/j.cbi.2016.09.006
  36. The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases vol.11, 2017, https://doi.org/10.3389/fnins.2017.00254
  37. Using the Gene Ontology to Annotate Key Players in Parkinson’s Disease vol.14, pp.3, 2016, https://doi.org/10.1007/s12021-015-9293-2
  38. Lysosomal Storage Diseases-Regulating Neurodegeneration vol.9s2, 2015, https://doi.org/10.4137/JEN.S25475
  39. Targeting Cellular Stress Mechanisms and Metabolic Homeostasis by Chinese Herbal Drugs for Neuroprotection vol.23, pp.2, 2018, https://doi.org/10.3390/molecules23020259
  40. Aberrant regulation of autophagy in mammalian diseases vol.14, pp.1, 2018, https://doi.org/10.1098/rsbl.2017.0540
  41. Modulating cellular autophagy for controlled antiretroviral drug release vol.13, pp.17, 2018, https://doi.org/10.2217/nnm-2018-0224
  42. Structural insights into pro-aggregation effects of C. elegans CRAM-1 and its human ortholog SERF2 vol.8, pp.1, 2018, https://doi.org/10.1038/s41598-018-33143-1
  43. Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches vol.8, pp.9, 2018, https://doi.org/10.3390/brainsci8090177
  44. Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond vol.19, pp.8, 2018, https://doi.org/10.3390/ijms19082423
  45. GLP-1 Analogue Liraglutide Attenuates Mutant Huntingtin-Induced Neurotoxicity by Restoration of Neuronal Insulin Signaling vol.19, pp.9, 2018, https://doi.org/10.3390/ijms19092505
  46. Corni Fructus: a review of chemical constituents and pharmacological activities vol.13, pp.1, 2018, https://doi.org/10.1186/s13020-018-0191-z
  47. Mechanism and medical implications of mammalian autophagy vol.19, pp.6, 2018, https://doi.org/10.1038/s41580-018-0003-4
  48. Dopamine Receptor Subtypes Differentially Regulate Autophagy vol.19, pp.5, 2018, https://doi.org/10.3390/ijms19051540
  49. Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer’s disease mouse models vol.11, pp.1, 2018, https://doi.org/10.1186/s13041-018-0364-9
  50. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines vol.9, pp.1664-3224, 2018, https://doi.org/10.3389/fimmu.2018.00586
  51. Molecular Regulation Mechanisms and Interactions Between Reactive Oxygen Species and Mitophagy vol.38, pp.1, 2019, https://doi.org/10.1089/dna.2018.4348
  52. The Role of Beclin-1 Acetylation on Autophagic Flux in Alzheimer’s Disease pp.1559-1182, 2019, https://doi.org/10.1007/s12035-019-1483-8
  53. The Role of PI3K/Akt and ERK in Neurodegenerative Disorders pp.1476-3524, 2019, https://doi.org/10.1007/s12640-019-0003-y
  54. The Effect of Fucoidan on Cellular Oxidative Stress and the CatD-Bax Signaling Axis in MN9D Cells Damaged by 1-Methyl-4-Phenypyridinium vol.10, pp.1663-4365, 2018, https://doi.org/10.3389/fnagi.2018.00429
  55. A Therapeutic Target for Inhibition of Neurodegeneration: Autophagy vol.47, pp.9, 2015, https://doi.org/10.1007/s11055-017-0519-7
  56. Emerging role of mitophagy in human diseases and physiology vol.50, pp.6, 2017, https://doi.org/10.5483/bmbrep.2017.50.6.056
  57. Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot vol.40, pp.9, 2015, https://doi.org/10.14348/molcells.2017.0151
  58. Protein SUMOylation modification and its associations with disease vol.7, pp.10, 2015, https://doi.org/10.1098/rsob.170167
  59. A Structural View of Xenophagy, a Battle between Host and Microbes vol.41, pp.1, 2018, https://doi.org/10.14348/molcells.2018.2274
  60. A Molecular Approach to Mitophagy and Mitochondrial Dynamics vol.41, pp.1, 2015, https://doi.org/10.14348/molcells.2018.2277
  61. Crosstalk between MicroRNAs and Autophagy in Adult Neurogenesis: Implications for Neurodegenerative Disorders vol.3, pp.2, 2015, https://doi.org/10.3233/bpl-180066
  62. 정상 및 atg5 유전자 제거 섬유아세포에서 자가포식체의 미세구조 및 이들의 정량적 분석 vol.31, pp.5, 2018, https://doi.org/10.5806/ast.2018.31.5.208
  63. The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux vol.9, pp.None, 2015, https://doi.org/10.1038/s41598-019-40887-x
  64. Autophagy inducing cyclic peptides constructed by methionine alkylation vol.55, pp.29, 2015, https://doi.org/10.1039/c9cc01027k
  65. Cubeben induces autophagy via PI3K-AKT-mTOR pathway to protect primary neurons against amyloid beta in Alzheimer’s disease vol.71, pp.3, 2019, https://doi.org/10.1007/s10616-019-00313-6
  66. A novel transgenic zebrafish line allows for in vivo quantification of autophagic activity in neurons vol.15, pp.8, 2015, https://doi.org/10.1080/15548627.2019.1580511
  67. The Effects of 8-Week Endurance Training on Prostatic Autophagy and Benign Prostatic Hyperplasia of Rats vol.28, pp.3, 2019, https://doi.org/10.15857/ksep.2019.28.3.270
  68. On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective vol.9, pp.11, 2015, https://doi.org/10.3390/biom9110690
  69. Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington’s pathology in zQ 175 mice vol.12, pp.None, 2015, https://doi.org/10.1186/s13041-019-0456-1
  70. MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy vol.42, pp.1, 2015, https://doi.org/10.1007/s13258-019-00881-z
  71. A new avenue for treating Parkinson's disease targeted at aggrephagy modulation and neuroinflammation: Insights from in vitro and animal studies vol.51, pp.None, 2015, https://doi.org/10.1016/j.ebiom.2019.11.036
  72. Nix Plays a Neuroprotective Role in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats vol.14, pp.None, 2015, https://doi.org/10.3389/fnins.2020.00245
  73. Targeting autophagy-related protein kinases for potential therapeutic purpose vol.10, pp.4, 2020, https://doi.org/10.1016/j.apsb.2019.10.003
  74. mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent vol.3, pp.2, 2015, https://doi.org/10.1021/acsptsci.0c00013
  75. Recent Progress of Nanomedicine in the Treatment of Central Nervous System Diseases vol.3, pp.5, 2015, https://doi.org/10.1002/adtp.201900159
  76. PARP1 Impedes SIRT1-Mediated Autophagy during Degeneration of the Retinal Pigment Epithelium under Oxidative Stress vol.43, pp.7, 2015, https://doi.org/10.14348/molcells.2020.0078
  77. Dysregulation of TFEB contributes to manganese-induced autophagic failure and mitochondrial dysfunction in astrocytes vol.16, pp.8, 2015, https://doi.org/10.1080/15548627.2019.1688488
  78. The Dichotomous Role of Extracellular Vesicles in the Central Nervous System vol.23, pp.9, 2020, https://doi.org/10.1016/j.isci.2020.101456
  79. Utility of Reactive Species Generation in Plasma Medicine for Neuronal Development vol.8, pp.9, 2015, https://doi.org/10.3390/biomedicines8090348
  80. Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders vol.26, pp.6, 2015, https://doi.org/10.1007/s13365-020-00906-4
  81. Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer’s disease model mice in a sex-selective manner vol.13, pp.662, 2015, https://doi.org/10.1126/scisignal.abd2494
  82. A novel autophagy‐related lncRNA prognostic risk model for breast cancer vol.25, pp.1, 2015, https://doi.org/10.1111/jcmm.15980
  83. Autophagy and heat: a potential role for heat therapy to improve autophagic function in health and disease vol.130, pp.1, 2021, https://doi.org/10.1152/japplphysiol.00542.2020
  84. A Novel Autophagy-Related lncRNA Prognostic Signature Associated with Immune Microenvironment and Survival Outcomes of Gastric Cancer Patients vol.14, pp.None, 2015, https://doi.org/10.2147/ijgm.s331959
  85. Gut Microbiome Regulation of Autophagic Flux and Neurodegenerative Disease Risks vol.12, pp.None, 2015, https://doi.org/10.3389/fmicb.2021.817433
  86. To betray or to fight? The dual identity of the mitochondria in cancer vol.17, pp.6, 2015, https://doi.org/10.2217/fon-2020-0362
  87. Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet vol.15, pp.None, 2015, https://doi.org/10.3389/fncel.2021.733607
  88. The H+-ATPase (V-ATPase): from proton pump to signaling complex in health and disease vol.320, pp.3, 2015, https://doi.org/10.1152/ajpcell.00442.2020
  89. The Secrets of Alternative Autophagy vol.10, pp.11, 2015, https://doi.org/10.3390/cells10113241
  90. Autophagy and apoptosis cascade: which is more prominent in neuronal death? vol.78, pp.24, 2015, https://doi.org/10.1007/s00018-021-04004-4
  91. Mitochondrial connections with immune system in Zebrafish vol.2, pp.None, 2015, https://doi.org/10.1016/j.fsirep.2021.100019
  92. A novel autophagy-related genes prognostic risk model and validation of autophagy-related oncogene VPS35 in breast cancer vol.21, pp.1, 2015, https://doi.org/10.1186/s12935-021-01970-4
  93. Unfolding the role of autophagy in the cancer metabolism vol.28, pp.None, 2015, https://doi.org/10.1016/j.bbrep.2021.101158
  94. GPNMB mitigates Alzheimer’s disease and enhances autophagy via suppressing the mTOR signal vol.767, pp.None, 2022, https://doi.org/10.1016/j.neulet.2021.136300