• BMB Reports
• /
• 제43권4호
• /
• pp.233-244
• /
• 2010

Parkinson's disease (PD) is the second most common neurodegenerative disease, and 5-10% of the PD cases are genetically inherited as familial PD (FPD). LRRK2 (leucine-rich repeat kinase 2) was first reported in 2004 as a gene corresponding to PARK8, an autosomal gene whose dominant mutations cause familial PD. LRRK2 contains both active kinase and GTPase domains as well as protein-protein interaction motifs such as LRR (leucine-rich repeat) and WD40. Most pathogenic LRRK2 mutations are located in either the GTPase or kinase domain, implying important roles for the enzymatic activities in PD pathogenic mechanisms. In comparison to other PD causative genes such as parkin and PINK1, LRRK2 exhibits two important features. One is that LRRK2's mutations (especially the G2019S mutation) were observed in sporadic as well as familial PD patients. Another is that, among the various PD-causing genes, pathological characteristics observed in patients carrying LRRK2 mutations are the most similar to patients with sporadic PD. Because of these two observations, LRRK2 has been intensively investigated for its pathogenic mechanism (s) and as a target gene for PD therapeutics. In this review, the general biochemical and molecular features of LRRK2, the recent results of LRRK2 studies and LRRK2's therapeutic potential as a PD target gene will be discussed.

• The Korean Journal of Pain
• /
• 제33권1호
• /
• pp.90-96
• /
• 2020

Background: Parkinson's disease (PD) is a neurodegenerative disorder that is the second most common disorder after Alzheimer's disease. PD includes both "motor" and "non-motor" symptoms, one of which is pain. The aim of this study was to investigate the clinical characteristics of pain in patients with PD. Methods: This cross-sectional study included 250 patients diagnosed with PD, 70% of which had mild to moderate PD (stages 2/3 of Hoehn and Yahr scale). The average age was 67.4 years, and the average duration since PD diagnosis was 7.1 years. Relevant data collected from PD patients were obtained from their personal medical history. Results: The prevalence of pain was found to be high (82%), with most patients (79.2%) relating their pain to PD. Disease duration was correlated with the frequency of intense pain (R: 0.393; P < 0.05). PD pain is most frequently perceived as an electrical current (64%), and two pain varieties were most prevalent (2.60 ± 0.63). Our findings confirm links between pain, its evolution over time, its multi-modal character, the wide variety of symptoms of PD, and the female sex. Conclusions: Our results demonstrated that the pain felt by PD patients is mainly felt as an electrical current, which contrasts with other studies where the pain is described as burning and itching. Our classification is innovative because it is based on anatomy, whereas those of other authors were based on syndromes.

• Journal of Acupuncture Research
• /
• 제36권2호
• /
• pp.113-117
• /
• 2019

Parkinson's disease (PD) is a neurodegenerative disease, where treatment with medication may lead to gastrointestinal (GI) symptoms. The objective of this case study was to investigate the effectiveness of Korean medicine (KM) in treating PD with drug-induced GI dysfunction. A 70-year-old female participant was diagnosed with PD in 2010 and drug-induced gastritis in 2016. Her major symptoms were related to GI, PD, and overall feeling of weakness. She was treated with KM including pharmacopuncture, acupuncture, moxibustion, and herbal medicines, in combination with Western medicines during 46 days of in-patient care. This study showed an improvement in symptoms and scores on the GI symptom scale, Unified Parkinson's disease rating scale, Hoehn and Yahr staging, Berg balance scale, PD quality of life, and stress index at discharge. This case demonstrated that the symptoms of drug-induced GI dysfunctions in PD was improved by treatment with KM.

• BMB Reports
• /
• 제48권5호
• /
• pp.243-248
• /
• 2015

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing evidence is suggesting that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and the carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to the yet unknown diverse functions of LRRK2. Here, we reviewed current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discussed the possibility of targeting LRRK2 in such diseases. [BMB Reports 2015; 48(5): 243-248]

• BMB Reports
• /
• 제52권6호
• /
• pp.349-359
• /
• 2019

After the first research declaring the generation of human induced pluripotent stem cells (hiPSCs) in 2007, several attempts have been made to model neurodegenerative disease in vitro during the past decade. Parkinson's disease (PD) is the second most common neurodegenerative disorder, which is mainly characterized by motor dysfunction. The formation of unique and filamentous inclusion bodies called Lewy bodies (LBs) is the hallmark of both PD and dementia with LBs. The key pathology in PD is generally considered to be the alpha-synuclein (${\alpha}$-syn) accumulation, although it is still controversial whether this protein aggregation is a cause or consequence of neurodegeneration. In the present work, the recently published researches which recapitulated the ${\alpha}$-syn aggregation phenomena in sporadic and familial PD hiPSC models were reviewed. Furthermore, the advantages and potentials of using patient-derived PD hiPSC with focus on ${\alpha}$-syn aggregation have been discussed.

• 대한한방내과학회지
• /
• 제41권1호
• /
• pp.59-68
• /
• 2020

Objectives: The purpose of this study was to investigate the current state of clinical trials for acupuncture treatment of Parkinson's disease (PD) using neuroimaging methods. Methods: We searched for clinical trial studies of acupuncture treatment for Parkinson's disease that used neuroimaging methods in the MEDLINE (PubMed) database. The identified studies were then selected manually based on inclusion criteria. We subsequently analyzed the characteristics of the selected articles and reviewed the neural substrates of acupuncture treatment in PD. Results: Eight studies were included. The most frequently applied modality for PD was functional MRI. The most frequently selected acupoint for PD was GV34. Several studies showed that acupuncture treatment could improve the symptoms of PD. Through the analysis, we demonstrated that the neuroimaging method could capture the neural substrates associated with PD and that acupuncture treatment may affect the activation of brain areas that are impaired in PD in a different way than sham acupuncture. Conclusions: Applying a neuroimaging method could be helpful in clinical trials of acupuncture treatment for PD, and more efforts should be made in this area.

• 대한정형도수물리치료학회지
• /
• 제8권2호
• /
• pp.73-87
• /
• 2002

Parkinson's disease(PD) is a progressive neurodegenerative disease that affects the functioning of the basal ganglia, a brain area that contributes to the control of movement. The disease is caused by the death of nerve cells in the brain that produce dopamine, a chemical messenger. The cells affected usually produce a neurotransmitter(a chemical that transmits nerver impulses) called dopamine, which acts with acetylcholine, another neurotransmitter, to fine-tune muscle control. In Parkinson's disease, the level of dopamine relative to acetylcholine is reduced, adversely affecting muscle control. When the supply of dopamine is depleted, the function of the basal ganglia is disrupted and its ability to control movement deteriorates. The result is that PD patients experience moderate rigidity, difficulty in initiating movements and slowness in executing them, and a rhythmical tremor at rest. Although the cause of Parkinson's disease is not known, genetic factors may be involved. About 3 in 10 people with the disorder have an affected family member. About 1 in 100 people over the age of 60 in the US have Parkinson's disease. And Parkinson's disease is slightly more common in men. The course of the disease is variable, but drugs may be the best effective in treating the symptoms and improving quality of life. But, The doctor may arrange physical therapy to help with physical mobility problems. It is important to continue to exercise and take care of your general health. Try to take a walk each day. Stretching exercises can help you maintain your strength and mobility. So, This papers will serve about the information of PD for clinical physical therapist. Finally, The aim of review is increasing approach method and technique for PD patients by the view of physical therapy.

• Nutrition Research and Practice
• /
• 제11권2호
• /
• pp.114-120
• /
• 2017

BACKGROUND/OBJECTIVES: A pivotal role of oxidative stress has been emphasized in the pathogenesis as well as in the disease progression of Parkinson's disease (PD). We aimed at investigating serum levels of antioxidant vitamins and elucidating whether they could be associated with the pathogenesis and progression of PD. MATERIALS/METHODS: Serum levels of retinol, ${\alpha}$- and ${\gamma}$-tocopherols, ${\alpha}$- and ${\beta}$-carotenes, lutein, lycopene, zeaxanthin and ${\beta}$-cryptoxanthin were measured and compared between 104 patients with idiopathic PD and 52 healthy controls matched for age and gender. In order to examine the relationship between antioxidant vitamins and the disease progression, multiple group comparisons were performed among the early PD (Hoehn and Yahr stage I and II, N = 47), advanced PD (stage III and IV, N = 57) and control groups. Separate correlation analyses were performed between the measured antioxidant vitamins and clinical variables, such as Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) motor score. RESULTS: Compared to controls, PD patients had lower levels of ${\alpha}$- and ${\beta}$-carotenes and lycopene. ${\alpha}$-carotene, ${\beta}$-carotene and lycopene levels were significantly reduced in advanced PD patients relative to early PD patients and were negatively correlated with Hoehn and Yahr stage and UPDRS motor score in PD patients. No significant differences were found in serum levels of retinol, ${\alpha}$- and ${\gamma}$-tocopherols, and other carotenoids between PD patients and controls. No significant correlations were found between these vitamin levels and clinical variables in PD patients. CONCLUSTIONS: We found that serum levels of some carotenoids, ${\alpha}$-carotene, ${\beta}$-carotene and lycopene, were lower in PD patients, and that these carotenoids inversely correlated with clinical variables representing disease progression. Our findings suggest that decreases in serum ${\alpha}$-carotene, ${\beta}$-carotene and lycopene may be associated with the pathogenesis as well as progression of PD.

• 대한간호학회지
• /
• 제40권4호
• /
• pp.580-588
• /
• 2010

Purpose: The purpose of this study was to examine effects of decreased locomotor activity on mass, Type I and II fiber cross-sectional areas of ipsilateral and contralateral hindlimb muscles 21 days after establishing the Parkinson's disease rat model. Methods: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 50 ${mu}g$) into the left substantia nigra after stereotaxic surgery. Adult male Sprague-Dawley rats were assigned to one of two groups; the Parkinson's disease group (PD; n=17) and a sham group (S; n=8). Locomotor activity was assessed before and 21 days after the experiment. At 22 days after establishing the rat model, all rats were anesthetized and soleus and plantaris muscles were dissected from both ipsilateral and contralateral sides. The brain was dissected to identify dopaminergic neuronal death of substantia nigra in the PD group. Results: The PD group at 21 days after establishing the Parkinson's disease rat model showed significant decrease in locomotor activity compared with the S group. Weights and Type I and II fiber cross-sectional areas of the contralateral soleus muscle of the PD group were significantly lower than those of the S group. Conclusion: Contralateral soleus muscle atrophy occurs 21 days after establishing the Parkinson's disease rat model.

• Interdisciplinary Bio Central
• /
• 제4권3호
• /
• pp.6.1-6.12
• /
• 2012

Parkinson's disease (PD) is a complicated neurodegenerative disorder although it is oftentimes defined by clinical motor symptoms originated from age dependent and progressive loss of dopaminergic neurons in the midbrain. The pathogenesis of PD involves dopaminergic and nondopaminergic neurons in many brain regions and the molecular mechanisms underlying the death of different cell types still remain to be elucidated. There are indications that PD causing disease processes occur in a global scale ranging from DNA to RNA, and proteins. Several PD-associated genes have been reported to play diverse roles in controlling cellular functions in different levels, such as chromatin structure, transcription, processing of mRNA, translational modulation, and posttranslational modification of proteins. The advent of quantitative high throughput screening (HTS) tools makes it possible to monitor systemic changes in DNA, RNA and proteins in PD models. Combined with dopamine neuron isolation or derivation of dopamine neurons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonologies will provide opportunities to draw PD causing sequences of molecular events in pathologically relevant PD samples. Here I discuss previous studies that identified molecular functions in which PD genes are involved, especially those signaling pathways that can be efficiently studied using HTS methodologies. Brief descriptions of quantitative and systemic tools looking at DNA, RNA and proteins will be followed. Finally, I will emphasize the use and potential benefits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegneration in PD.