10 results on '"Lin, Han-I"'
Search Results
2. Generation of induced pluripotent stem cells (IBMSi011-A) from a patient with Parkinson's disease carrying LRRK2 p.I1371V mutation.
- Author
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Lin HI, Cheng YC, Ko HW, Wen CH, Lu HE, Huang CY, Hsieh PCH, and Lin CH
- Subjects
- Animals, Cells, Cultured, Cellular Reprogramming, Female, Humans, Induced Pluripotent Stem Cells metabolism, Leukocytes, Mononuclear metabolism, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged, Parkinson Disease pathology, Phenotype, Teratoma pathology, Cell Differentiation, Induced Pluripotent Stem Cells pathology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Leukocytes, Mononuclear pathology, Mutation, Parkinson Disease genetics, Teratoma etiology
- Abstract
Leucine rich repeat kinase 2 (LRRK2) is the causative gene for autosomal-dominant familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with LRRK2 c.4111A > G (p.I1371V) mutation by using the Sendai-virus delivery system. The resulting iPSCs had a normal karyotype. The iPSCs also showed pluripotency confirmed by immunofluorescent staining and differentiated into the three germ layers in vivo. This cellular model will provide a platform for studying the role of LRRK2 in the disease process., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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3. PDE8B mutation is not associated with Parkinson's disease in a Taiwanese population.
- Author
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Fan TS, Wu RM, Lin HI, Cheng C, and Lin CH
- Subjects
- Adult, Aged, Aged, 80 and over, Asian People genetics, Genetic Association Studies, High-Throughput Nucleotide Sequencing, Humans, Middle Aged, Mutation, Taiwan, 3',5'-Cyclic-AMP Phosphodiesterases genetics, Parkinson Disease genetics
- Abstract
Mutations in the phosphodiesterase 8B gene (PDE8B) were recently linked to autosomal-dominant striatal degeneration clinically presenting as slowly progressive parkinsonism. PDE8B degrades cyclic adenosine monophosphate (cAMP), a second messenger involved in dopamine signaling. Dopamine deficiency is the pathognomonic feature of Parkinson's disease (PD). Few studies have explored the role of PDE8B in PD. We aim to address the genetic contribution of PDE8B in early-onset and familial PD in a Taiwanese population. Among 642 participants, we sequenced the exon containing previously reported mutations and exon-intron boundaries of PDE8B in 196 PD pedigrees without known PD-causative gene mutations, 207 patients with early-onset PD (age of onset <50 years), and 239 ethnicity-matched controls. We did not find any coding variants or previously reported mutations, suggesting that PDE8B mutations are not a common cause of familial or early-onset PD in this Taiwanese population., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
4. Catechol-O-methyltransferase (COMT) genetic variants are associated with cognitive decline in patients with Parkinson's disease.
- Author
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Lin CH, Fan JY, Lin HI, Chang CW, and Wu YR
- Subjects
- Aged, Cognitive Dysfunction etiology, Cognitive Dysfunction physiopathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Parkinson Disease complications, Parkinson Disease physiopathology, Taiwan, Catechol O-Methyltransferase genetics, Cognitive Dysfunction genetics, Parkinson Disease genetics
- Abstract
Objective: Catechol-O-methyltransferase (COMT), an enzyme that catalyzes the degradation of dopamine, is necessary for both motor and cognitive functions. Few studies have examined the association between COMT variants and cognition in patients with Parkinson's disease (PD)., Methods: We assessed a cohort of 409 PD patients without dementia who were regularly followed for two years. The Unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE) were administered at baseline and during the follow-up. The genetic variants and haplotypes of COMT, including rs6267, rs6269, rs4633, rs4818, and rs4680, were examined., Results: No association was observed between COMT genotypes and baseline cognitive function. After a mean follow-up period of 647.3 days, MMSE scores deteriorated with age. Cognitive decline correlated with age (P < 0.05) but not with the motor severity defined using UPDRS part III scores (P = 0.21). Kaplan-Meier survival analyses showed that PD patients carrying the G allele of the rs6269 variant and COMT haplotypes constituting the G allele of rs6269 showed a significantly more rapid decline in the MMSE scores over the follow-up period (log-rank test, P < 0.01). Cox proportional regression analysis adjusted for covariates revealed that among patients with PD, those carrying the high-COMT activity haplotype (G_C_C_G for rs6269, rs4633, rs4818, and rs4680) showed a high risk of cognitive decline (hazard ratio = 3.24; P = 0.02)., Conclusion: Our findings suggest that the high-COMT activity haplotype is associated with cognitive decline in patients with PD., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
5. Generation of 2 induced pluripotent stem cell lines derived from patients with Parkinson's disease carrying LRRK2 G2385R variant.
- Author
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Cheng YC, Huang CY, Ho MC, Hsu YH, Syu SH, Lu HE, Lin HI, Lin CH, and Hsieh PCH
- Subjects
- Adult, Base Sequence, Cell Line, Humans, Male, Middle Aged, Reproducibility of Results, Cell Culture Techniques methods, Induced Pluripotent Stem Cells cytology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Mutation genetics, Parkinson Disease genetics, Parkinson Disease pathology
- Abstract
Leucine rich repeat kinase (LRRK2) is the most prevalent genetic cause for Parkinson's disease. LRRK2 p.G2385R is an Asian specific genetic risk factor for sporadic Parkinson's disease. We generated two induced pluripotent stem cells (iPSCs), IBMS-iPSC-018-09 and IBMS-iPSC-020-01, from the peripheral blood mononuclear cells of two patients carrying LRRK2 p.G2385R variant by using the Sendai-virus delivery system. These iPSCs had a normal karyotype and exhibited pluripotency, such as an embryonic stem cell-like morphology, expression of pluripotent markers, and capacity to differentiate into three germ layers. This cellular model will provide a platform for pathophysiological studies of neurodegeneration in Parkinson's disease., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
6. Depression and Catechol-O-methyltransferase (COMT) genetic variants are associated with pain in Parkinson's disease.
- Author
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Lin CH, Chaudhuri KR, Fan JY, Ko CI, Rizos A, Chang CW, Lin HI, and Wu YR
- Subjects
- Age of Onset, Aged, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, NAV1.7 Voltage-Gated Sodium Channel genetics, Pain Measurement, Receptors, Opioid, mu genetics, Severity of Illness Index, Catechol O-Methyltransferase genetics, Chronic Pain genetics, Depression complications, Parkinson Disease complications, Polymorphism, Single Nucleotide
- Abstract
Pain is a distressing symptom of Parkinson disease (PD). We aim to determine whether the genetic variants of chronic pain-related genes contribute to pain in PD patients. We included 418 PD patients and evaluated pain severity on King's PD pain scale. We genotyped rs6267, rs6269, rs4633, rs4818 and rs4680 of COMT, rs6746030 of SCN9A, and rs1799971 of OPRM1. In total, 193 participants (46.2%) experienced pain. Compared to pain-free PD patients, PD patients with pain had an earlier age of onset, longer disease duration, and higher depression and motor severity (P < 0.01). The frequencies of COMT rs4680 "A" allele were higher in PD patients with pain than those without pain (46.1% vs. 31.1%, P < 0.01). Pain severity was significantly associated with disease duration (P = 0.02), and COMT rs6267 T allele (P < 0.01). We stratified PD by status of depression and the association between COMT rs6267 "GT" genotype and pain severity remained significant (P < 0.01). Furthermore, pain severity was significantly higher in participants having COMT rs4680 "GG" and "GA" genpotypes than those having "AA" genotype (P = 0.04). We concluded that depression and COMT rs4680 "GG" and "GA" genotypes and COMT rs6267 "GT" genotype contribute to pain in PD patients.
- Published
- 2017
- Full Text
- View/download PDF
7. Lack of RAB39B mutations in early-onset and familial Parkinson's disease in a Taiwanese cohort.
- Author
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Lin HH, Wu RM, Lin HI, Chen ML, Tai CH, and Lin CH
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Asian People genetics, Chromosomes, Human, X genetics, Cohort Studies, Exons genetics, Female, Genes, Recessive, Humans, Introns genetics, Male, Middle Aged, Parkinson Disease epidemiology, Parkinson Disease metabolism, Parkinson Disease pathology, Taiwan epidemiology, Young Adult, alpha-Synuclein metabolism, Genetic Association Studies, Mutation, Parkinson Disease genetics, rab GTP-Binding Proteins genetics
- Abstract
Loss of function mutations in RAB39B were recently linked to X-linked recessive early-onset Parkinsonism with variable degrees of intellectual dysfunction. Postmortem examination of the brain biopsy from a patient carrying the gene deletion revealed widespread α-synuclein pathology. However, subsequent analyses reported conflict results to replicate the role of RAB39B mutations in patients with early-onset Parkinsonism. The aim of this study was to address the genetic contribution of RAB39B in early-onset and familial Parkinson's disease (PD) in a Taiwanese population. Among 466 subjects, we sequenced both the exons and exon-intron boundaries of RAB39B from 235 patients with early-onset PD (age of onset <50 years), 119 probands with familial PD, and 112 ethnicity-matched control subjects. We did not find any coding variants or previously reported mutations, suggesting that RAB39B mutations are not a common cause of early-onset or familial PD in our Taiwanese population., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
8. Lovastatin protects neurite degeneration in LRRK2-G2019S parkinsonism through activating the Akt/Nrf pathway and inhibiting GSK3β activity.
- Author
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Lin CH, Lin HI, Chen ML, Lai TT, Cao LP, Farrer MJ, Wu RM, and Chien CT
- Subjects
- Animals, Animals, Genetically Modified, Dopaminergic Neurons drug effects, Dopaminergic Neurons pathology, Drosophila melanogaster genetics, Glycogen Synthase Kinase 3 beta antagonists & inhibitors, Glycogen Synthase Kinase 3 beta biosynthesis, Humans, Lovastatin administration & dosage, Mice, Motor Neurons drug effects, Motor Neurons pathology, Mutation, Nerve Degeneration genetics, Nerve Degeneration pathology, Neurites drug effects, Parkinson Disease drug therapy, Parkinson Disease pathology, Parkinsonian Disorders drug therapy, Parkinsonian Disorders genetics, Parkinsonian Disorders physiopathology, Signal Transduction drug effects, Glycogen Synthase Kinase 3 beta genetics, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Nerve Degeneration drug therapy, Parkinson Disease genetics, Proto-Oncogene Proteins c-akt genetics, Serine Endopeptidases genetics
- Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder that lacks a disease-modifying therapy. Leucine-rich repeat kinase 2 (LRRK2) was implicated as the most common genetic cause of PD. We previously established a LRRK2-G2019S Drosophila model that displayed the crucial phenotypes of LRRK2 parkinsonism. Here, we used a two-step approach to identify compounds from the FDA-approved licensed drug library that could suppress neurite degeneration in LRRK2-G2019S parkinsonism. Of 640 compounds, 29 rescued neurite degeneration phenotypes and 3 restored motor disability and dopaminergic neuron loss in aged LRRK2-G2019S flies. Of these three drugs, lovastatin had the highest lipophilicity, which facilitated crossing the blood-brain barrier. In LRRK2-G2019S knock-in mice and stably transfected human dopaminergic cells, lovastatin significantly rescued neurite degeneration in a dose-dependent manner, within a range of 0.05-0.1 μm The beneficial effect of lovastatin was exerted by activating anti-apoptotic Akt/Nrf signaling and decreasing caspase 3 levels. We also observed that lovastatin inhibited GSK3β activity, a kinase downstream of Akt, by up-regulating GSK3β (Ser9) phosphorylation. This inhibition subsequently decreased tau phosphorylation, which was linked to neuronal cytoskeleton instability. Conversely, pre-treatment with the Akt inhibitor, A6730, blocked the lovastatin-induced neuroprotective effect. The rescuing effects of lovastatin in dendritic arborization of LRRK2-G2019S neurons were abolished by co-expressing either a mutant allele of Akt (Akt1
04226 ) or a constitutively active form of GSK3β (sggS9A ). Our findings demonstrated that lovastatin restored LRRK2-G2019S neurite degeneration by augmenting Akt/NRF2 pathway and inhibiting downstream GSK3β activity, which decreased phospho-tau levels. We suggested that lovastatin is a potential disease-modifying agent for LRRK2-G2019S parkinsonism., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)- Published
- 2016
- Full Text
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9. Vitamin D receptor genetic variants and Parkinson's disease in a Taiwanese population.
- Author
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Lin CH, Chen KH, Chen ML, Lin HI, and Wu RM
- Subjects
- Adult, Aged, Aged, 80 and over, Asian People, Case-Control Studies, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Parkinson Disease blood, Risk, Taiwan, Vitamin D blood, Parkinson Disease genetics, Polymorphism, Genetic, Receptors, Calcitriol genetics, Vitamin D physiology
- Abstract
Patients with Parkinson's disease (PD) have hypovitaminosis D status and genetic variants of vitamin D receptor (VDR) gene are recently shown to be associated with PD in a large-scale genome-wide association study in a Caucasian population. Few studies examined VDR genetic variants in large-scale Asian patients with PD. We therefore genotyped 6 VDR genetic variants in a total of 1492 Taiwanese subjects, including 700 patients with PD and 792 age and/or gender matched control subjects. We did not observe any significant associations between the studied genetic variants of VDR and the risk of PD. Our data suggest that genetic variations of the VDR gene did not play a major role in a Taiwanese PD population. Further studies of VDR and its interaction with serum vitamin D levels are warranted to clarify the potential role of vitamin D in PD pathogenesis., (Copyright © 2014. Published by Elsevier Inc.)
- Published
- 2014
- Full Text
- View/download PDF
10. The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease.
- Author
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Wu RM, Lin CH, and Lin HI
- Subjects
- Female, Humans, Male, Genetic Predisposition to Disease genetics, Mutation, Parkinson Disease genetics, Sphingomyelin Phosphodiesterase genetics
- Published
- 2014
- Full Text
- View/download PDF
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