• Title/Summary/Keyword: Parkinson

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Neuroprotective effects of Salacca wallichiana extract against glutamate-induced oxidative stress in mouse Hippocampal HT22 cells (쥐 해마 HT22 세포에서 글루타메이트 유도 산화 스트레스에 대한 Salacca wallichiana 추출물의 신경 보호 효과)

  • Ji Hun Byeon;Ye Yeong Hong;Jungwhoi Lee;Thet Thet Mar Win;Su Su Hlaing;Song-I Han;Jae Hoon Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.250-257
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    • 2023
  • Glutamate is an excitatory neurotransmitter distributed in the central nervous system of mammals. However, high concentrations of glutamate are known to cause neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and stroke by causing nerve cell death. In this study, the antioxidant activity and neuroprotective effect of subtropical natural products were analyzed. Among 11 subtropical plant extracts mainly tested, Sallacca wallichiana extract (SE) showed the greatest free radical scavenging activity. Then, we confirmed through WST-1 assay that SE protected HT22 cells against glutamate-induced cell death in a concentration-dependent manner. The protective effects of SE against glutamate-induced apoptosis in HT22 cells were also confirmed by flow cytometry analysis using Annexin V/PI double staining. We also confirmed using H2DCF-DA single staining that SE inhibits glutamate-induced intracellular reactive oxygen species. And we were confirmed through that SE inhibited glutamate-induced phosphorylation of Mitogen-activated Protein kinases. Consequently, our results propose that SE may contribute to the development of therapeutics to prevent neurodegenerative diseases.

Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition

  • Saewhan Park;Kyung-Hee Kim;Yun-Hee Bae;Young Taek Oh;Hyemi Shin;Hyung Joon Kwon;Chan Il Kim;Sung Soo Kim;Hwan-Geun Choi;Jong Bae Park;Byoung Dae Lee
    • International Journal of Stem Cells
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    • v.17 no.3
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    • pp.319-329
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    • 2024
  • Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

In Vitro Antioxidant Activity and Anticonvulsant Properties on Zebrafish PTZ-Induced Seizure Model of a Tilia viridis Aqueous Extract

  • Elina Malen Saint Martin;Ayelen Morena Sosa;Carolina Soledad Martinez;Jimena Prieto;Carla Marrassini;Cecilia Beatriz Dobrecky;Maria Rosario Alonso;Claudia Anesini
    • Journal of Pharmacopuncture
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    • v.27 no.3
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    • pp.211-222
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    • 2024
  • Objectives: Tilia viridis (Bayer) Simonk. (Malvaceae) is widely distributed in Argentina and employed for its tranquilizing properties. Other species of the genus (Tilia europaea L., Tilia cordata Mill., Tilia platyphyllos Scop.) have been traditionally used for the treatment of epilepsy. Epilepsy affects approximately 65 million people worldwide and is characterized by an imbalance between excitatory and inhibitory processes in the brain, leading to unpredictable, unprovoked, recurrent seizures. Current pharmacological interventions often present mild to moderately severe side effects. Epilepsy has been associated with oxidative and nitrative stress as well as neuroinflammation. Herbal medicine therapies may offer new treatment options with multi-target antioxidant and anticonvulsant effects for patients whose seizures remain uncontrolled, potentially providing cost-effective solutions for individuals worldwide suffering from uncontrolled epilepsy.The aim of this study was to demonstrate the anticonvulsant activity of a standardized T. viridis aqueous extract (TE). Methods: Study of the constituents of TE, TE's antioxidant and anticonvulsant activities and toxicity, and analysis of the possible relation between the potential activities and the compounds present in the extract. In order to demonstrate TE's anticonvulsant activity a zebrafish model was used. The study also assessed TE's toxicity and antioxidant activity. To standardize the extract, total polyphenols and flavonoids were quantified and specific flavonoids were identified and quantified using HPLC-MS/MS and HPLC-UV. Results: TE exhibited anticonvulsant activity at low concentrations and demonstrated antioxidant effects by scavenging free radicals, exhibiting superoxide dismutase and peroxidase-like activities, as well as inhibiting lipoperoxidation. These actions can be attributed to the presence of polyphenols, particularly flavonoids. Conclusion: TE holds promise as a complementary herbal medicine in the treatment of epilepsy and may also offer benefits for other neuropathies associated with oxidative stress, such as Parkinson's disease and Alzheimer's disease.

Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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Status of health and nutritional intake of the elderly in long-term care facilities: focus on Gwangju Metropolitan City (노인의료복지시설 입소 노인의 건강 상태 및 영양소 섭취 현황: 광주광역시를 중심으로)

  • Han, Gyusang;Yang, Eunju
    • Journal of Nutrition and Health
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    • v.53 no.1
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    • pp.27-38
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    • 2020
  • Purpose: This study assessed the food intake and nutritional status of the elderly in long-term care facilities in order to provide adequate food services and improve the nutritional status. Methods: The survey was carried out from August 2019 to October 2019 for the elderly in long-term care facilities located in Gwangju Metropolitan City. The survey was conducted to collect data from 199 elderly persons (34 males and 165 females) aged over 65 years old. The food intake was assessed using a 1-day 24-hour recall method. Results: More than 90% of the subjects were over 75 years old. Forty five percent of the subjects were active, 44.2% of the subjects perceived themselves as not being healthy. Dementia and Parkinson's disease were the most common diseases, followed by hypertension, musculo-skeletal disease, diabetes, and stroke. Only 25.6% of the subjects had most of their teeth intact, and 44.7% of the subjects had difficulty in chewing and swallowing. The total food intake was 1,127 g in males and 1,078 g in females. The most frequently consumed foods were kimchi, cooked rice with multi-grains, soybean soup, cooked rice with white rice, yogurt, pumpkin porridge, soy milk, and duck soup. The average energy intake of the subjects was 1,564.9 kcal in males and 1,535.5 kcal in females. The overall nutritional status of the elderly in the long-term care facilities was poor. In particular, the intake of vitamin D and calcium, vitamin C, riboflavin, and potassium were very low. The intake of vitamin D was 5 ㎍, and 86.4% of the elderly were below the estimated average requirement, while the intake of sodium was high. Conclusion: The results of this study can be used to understand the health and nutritional status and to improve the food services and nutrition management for the elderly in longterm care facilities.

Usefulness of the Salivagram for the Diagnosis of Brain Lesions in Patients with Aspiration Pneumonia (뇌병변 환자에서 흡인성 폐렴 진단을 위한 Salivagram의 유용성)

  • Oh, Shin Hyun;Choi, Yung Sook;Ro, Dong Wook;Nam-Koong, Hyuk;Kim, Jae Sam;Leee, Chang Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.17 no.1
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    • pp.48-52
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    • 2013
  • Purpose: Bed, living a long time is required in adult patients with brain lesions such as stroke, traumatic brain injury, and Parkinson's disease, causing pneumonia and respiratory diseases may be due to aspiration of food or saliva. In patients with recurrent pneumonia or pulmonary symptoms, there is a need to determine the possibility of pulmonary aspiration due to aspiration of saliva. Materials and Methods: Saliva due to aspiration pneumonia diagnosis in patients with brain lesions request for inspection to the Department of Nuclear Medicine, 10 patients (male 6, female 4) were included in this study. Patients were fasted before the test, $^{99m}Tc_{O4}$ 185 MBq (5 mCi) of less than 1 mL of solution was administered in the oral cavity. Administration and 20 minutes of dynamic imaging acquisition, and immediately after that the static images were acquired. Delayed scan after 2-4 hours if necessary. Results: Positivity rate of all 10 patients was 60%. In 4 patients showed positive reactions after the administration of oral cavity in a 20-minute dynamic imaging were able to confirm whether the aspiration. In the remaining 2 patients, four hours of additional delay tests were able to confirm whether the aspiration. Conclusion: Does not require changes in patient posture compared to the other checks that can be diagnosed with aspiration pneumonia. A simple test and takes less time. Therefore be useful in providing information for the diagnosis and treatment modality.

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Thiobarbituric Acid Reactive Substances Levels in Brain Tissue of Aldh2 Knockout Mice Following Ethanol Exposure for 8 Weeks (Aldh2 knockout 마우스에서 8주간 에탄올 노출에 따른 뇌조직의 thiobarbituric acid reactive substances 농도)

  • Moon, Sun-In;Eom, Sang-Yong;Kim, Jung-Hyun;Yim, Dong-Hyuk;Kim, Hyong-Kyu;Kim, Yong-Dae;Kim, Heon
    • Journal of Life Science
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    • v.21 no.8
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    • pp.1163-1167
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    • 2011
  • Excessive alcohol consumption causes various degenerative brain diseases including Alzheimer's disease and Parkinson's disease. Absorbed ethanol is metabolized to acetaldehyde and acetic acid by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Acetaldehyde is well known as a toxicant through generation of reactive oxygen species (ROS). Therefore, ALDH2 activity may play important roles in the pathogenesis of alcohol-induced brain diseases. In this study, we demonstrated the effects of ALDH2 enzyme activity on lipid peroxidation in brain tissues and urine of mice exposed to ethanol for 8 weeks. Five male, 8-week old Aldh2 (+/+) and Aldh2 (-/-) mice (C57BL/6J strain) in each group were exposed to ethanol for 8 weeks (2 g/kg wt./day) using gavage, and those in the control group received 0.9% saline alone. Thiobarbituric acid reactive substances (TBARS) level, a marker for lipid peroxidation, was measured in whole brain tissue and urine by high performance liquid chromatography. As a result, chronic ethanol treatment did not show any statistical change on the TBARS level of brain tissue in both Aldh2 (+/+) mice and in Aldh2 (-/-) mice. However, following ethanol exposure for 8 weeks in Aldh2 (-/-) mice, the urinary TBARS levels were significantly increased to more than double compared to the pretreatment group. This result was not observed in Aldh2 (+/+) mice. These results suggest that although ALDH2 enzyme activity plays a role in the generation of ROS in the whole body, it does not seem to be important in the pathogenesis of alcohol induced degenerative brain diseases.

Inhibitory Effects of Asparagus cochinchinensis in LPS-Stimulated BV-2 Microglial Cells through Regulation of Neuroinflammatory Mediators, the MAP Kinase Pathway, and the Cell Cycle (Lipopolysaccharide로 자극된 BV-2 미세교세포에서 신경염증 매개체, MAP kinase경로, 세포주기의 조절에 의한 천문동(Asparagus cochinchinensis)의 저해효과)

  • Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
    • Journal of Life Science
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    • v.30 no.4
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    • pp.331-342
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

Different Metabolic Patterns of Parkinsonism: Analysed by Statistical Parametric Mapping (통계적 파라미터를 이용한 Parkinsonism의 Metabolic pattern 분석)

  • 주라형;김재승;최보영;문대혁;서태석
    • Progress in Medical Physics
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    • v.14 no.2
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    • pp.108-123
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    • 2003
  • The purpose of this study is to evaluate the contribution of $^{18}$ F-FDG brain PET in the differentiating Idiopathic parkinson's diesease (IPD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). We studied 24 patients with parkinsonism : 8 patients (mean age 67.9$\pm$10.7 y: M/F : 3/5) with IPD, 9 patients (57.9$\pm$9.2 y : M/F : 4/5) with MSA and 7 patients (67.6$\pm$4.8 y : M/F 3/4) with PSP. All patients with parkinsonism and 22 age-matched normal controls underwent $^{18}$ F FDG PET in 3D mode after the injection of 370 MBq $^{118}$ F FDG. The patients with IPD, MSh and PSP were compared with a normal control group by a two-sided t-test of SPM99 (uncorrected P<0.001, extent threshold>100 voxel). All three parkinsonism groups, showed significant hypometabolism in the cerebral neocortex compared to the normal control group. However, the three groups displayed different metabolism in the subcortical structure, brain stem, and cerebellum. In IPD, there was no significant hypometabolism in the putamen, brain stem and cerebellum. However, MSA patients showed significant hypometabolism in the striatum, pons, and cerebellum compared to the normal controls and IPD patients. In addition, PSP showed significant hypometabolism in the caudate nuclei, the thalamus, midbrain, and the cingulate gyrus compared to the normal controls, the IPD, and MSA groups (IPD vs Normal sensitivity/specificity : 75%/l00%, MSA vs Normal sensitivity/specificity :100%/87%, PSP vs Normal sensitivity/specificity : 86%/94%). Our results show that the regional metabolism of IPD, MSA, and PSP is different mainly in the striatum, thalamus, brain stem and cerebellum. An assessment of the $^{18}$ F-FDG PET scan images using SPM may be a useful adjunct to a clinical examination in making a differential diagnosis of Parkinsonism.

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Anti-neuroinflammatory Effect of Teleogryllus emma Derived Teleogryllusine in LPS-stimulated BV-2 Microglia (BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과)

  • Seo, Minchul;Shin, Yong Pyo;Lee, Hwa Jeong;Baek, Minhee;Lee, Joon Ha;Kim, In-Woo;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.30 no.11
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    • pp.999-1006
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    • 2020
  • The suppression of neuroinflammatory responses in microglial cells, well known as the main immune cells in the central nervous system (CNS), are considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Teleogryllus emma is widely consumed around the world for its broad-spectrum therapeutic effect. In a previous work, we performed transcriptome analysis on T. emma in order to obtain the diversity and activity of its antimicrobial peptides (AMPs). AMPs are found in a variety of species, from microorganisms to mammals. They have received much attention as candidates oftherapeutic drugs for the treatment of inflammation-associated diseases. In this study, we investigated the anti-neuroinflammatory effect of Teleogryllusine (VKWKRLNNNKVLQKIYFVKI-NH2) derived from T. emma on lipopolysaccharide (LPS) induced BV-2 microglia cells. Teleogryllusine significantly inhibited nitric oxide (NO) production without cytotoxicity, and reducing pro-inflammatory enzymes expression such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, Telegryllusine also inhibited the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) through down-regulation of the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathway. These results suggest that T. emma-derived Teleogryllusine could be a good source of functional substances that prevent neuroinflammation and neurodegenerative diseases.