scholarly journals VPS35, the core component of the retromer complex, and Parkinson's disease

Ibrain ◽  
2021 ◽  
Author(s):  
Ai‐Di Luo ◽  
Zu‐Cai Xu ◽  
Shu‐Sheng Liao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Core Component ◽  
The Core ◽  
Retromer Complex

Depression and Parkinson's Disease: Biological Therapies

2017 ◽  
Vol 41 (S1) ◽  
pp. S770-S770
Author(s):  
B. Mures ◽  
N.G. Lluis ◽  
A.P. Iñigo ◽  
M.H. German ◽  
T.G. Miriam ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychiatric Morbidity ◽  
Beneficial Effects ◽  
The Core ◽  
Previous Diagnosis ◽  
Medication Side ◽  
Dopaminergic Psychosis ◽  
Competing Interest ◽  
Motor Improvement

Introduction.Depression occurs in approximately 40% of patients with Parkinson's disease. Parkinson's disease is commonly associated with psychiatric morbidity, which includes depression, anxiety, and dopaminergic psychosis. These compound the patient's predicament. Fortunately, a variety of effective treatments are available.Objective.The purpose of this e-poster is to provide an update of the research regarding depression in Parkinson's disease.Methods.Describe a case report. A 56-year-old man, with previous diagnosis of Parkinson's disease. We used SSRIs, but they was not enough to successful treatment so we decided to use ECT.Results.Our patient failed to respond to medication or develop intolerable medication side effects. Electroconvulsive therapy (ECT) should be considered for this group of patients. Contrary to popular belief, ECT is a widely used and safe treatment for depression when medication fails. ECT has been shown to be effective and safe in PD for treating both depression and dopaminergic psychosis. Several studies also report varying periods of motor improvement following ECT in PD. A study is currently underway at UBC to examine this phenomenon in a controlled setting. ECT improves depression, may permit a reduction in antidepressant medications, and has intrinsic antiparkinsonian properties.Conclusions.ECT, has repeatedly been shown to have beneficial effects in PD, but has never gained acceptance as a clinical treatment option. We review the literature on the use of ECT in PD, pointing out that ECT has beneficial effects on both the core motor symptoms of PD as well as the commonly occurring psychiatric comorbidities.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals C. elegans genetic background modifies the core transcriptional response in an α-synuclein model of Parkinson’s disease

2018 ◽  
Author(s):  
Yiru A. Wang ◽  
Basten L. Snoek ◽  
Mark G. Sterken ◽  
Joost A.G. Riksen ◽  
Jana J. Stastna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Background ◽  
Expression Patterns ◽  
Transcriptional Response ◽  
Global Gene Expression ◽  
C Elegans ◽  
The Core ◽  
Repair Mechanisms

AbstractAccumulation of protein aggregates is a major cause of Parkinson’s disease (PD), a progressive neurodegenerative condition that is one of the most common causes of dementia. Transgenic Caenorhabditis elegans worms expressing the human synaptic protein α-synuclein show inclusions of aggregated protein and replicate the defining pathological hallmarks of PD. It is however not known how PD progression and pathology differs among individual genetic backgrounds. Here, we compared gene expression patterns, and investigated the phenotypic consequences of transgenic α-synuclein expression in five different C. elegans genetic backgrounds. Transcriptome analysis indicates that the effects of -synuclein expression on pathways associated with nutrient storage, lipid transportation and ion exchange depend on the genetic background. The gene expression changes we observe suggest that a range of phenotypes will be affected by α-synuclein expression. We experimentally confirm this, showing that the transgenic lines generally show delayed development, reduced lifespan, and an increased rate of matricidal hatching. These phenotypic effects coincide with the core changes in gene expression, linking developmental arrest, mobility, metabolic and cellular repair mechanisms to α-synuclein expression. Together, our results show both genotype-specific effects and core alterations in global gene expression and in phenotype in response to -synuclein. We conclude that the PD effects are substantially modified by the genetic background, illustrating that genetic background mechanisms should be elucidated to understand individual variation in PD.

scholarly journals Retromer dependent changes in cellular homeostasis and Parkinson’s disease

2021 ◽  
Author(s):  
Zhe Yang ◽  
Zebin Li ◽  
Rohan D. Teasdale
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Significant Role ◽  
Cellular Trafficking ◽  
Cellular Homeostasis ◽  
Retromer Complex ◽  
Endosomal System ◽  
Cargo Sorting

Abstract To date, mechanistic treatments targeting the initial cause of Parkinson’s disease (PD) are limited due to the underlying biological cause(s) been unclear. Endosomes and their associated cellular homeostasis processes have emerged to have a significant role in the pathophysiology associated with PD. Several variants within retromer complex have been identified and characterised within familial PD patients. The retromer complex represents a key sorting platform within the endosomal system that regulates cargo sorting that maintains cellular homeostasis. In this review, we summarise the current understandings of how PD-associated retromer variants disrupt cellular trafficking and how the retromer complex can interact with other PD-associated genes to contribute to the disease progression.

scholarly journals Blinded SAPS-PD Assessment After 10 Weeks of Pimavanserin Treatment for Parkinson’s Disease Psychosis

2020 ◽  
Vol 10 (4) ◽  
pp. 1389-1396
Author(s):  
Stuart H. Isaacson ◽  
Bruce Coate ◽  
James Norton ◽  
Srdjan Stankovic
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Controlled Trial ◽  
Previous Treatment ◽  
Open Label ◽  
Beneficial Effects ◽  
The Core ◽  
Open Label Extension ◽  
Core Study ◽  
Burden Scale

Background: Parkinson’s disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP. Objective: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study. Methods: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales. Results: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was – 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (–6.9 vs. –6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE. Conclusion: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.

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