Role of the VPS35 D620N mutation in Parkinson's disease |
| |
| Institution: | 1. Department of Neurology, University of Maryland School of Medicine, 110 South Paca Street, 3rd Floor, Baltimore, MD 21201, United States;2. Department of Epidemiology and Public Health, University of Maryland School of Medicine, 660 West Redwood Street, Howard Hall Suite 200, Baltimore, MD 21201, United States;1. University Medical Center Hamburg-Eppendorf (UKE), Department of Neurology, Hamburg, Germany;2. Department of Neurology, Ludwig-Maximilians-University, Munich, Germany;3. Sobell Department of Motor Neuroscience and Movement Disorders, Queen Square, UCL, London, United Kingdom;1. Research Centre for Healthy and Sustainable Living, Innovative Testing in Life Sciences and Chemistry, University of Applied Sciences, Heidelberglaan 7, 3584, CS, Utrecht, The Netherlands;2. Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703, HA, Wageningen, The Netherlands;3. Institute for Risk Assessment Sciences, Utrecht University, The Netherlands |
| |
| Abstract: | Parkinson's disease (PD) is a neurodegenerative disorder involving the loss of dopaminergic neurons in the brain. Following the discovery of the PD-causing D620N mutation in the VPS35 (Vacuolar sorting protein 35) gene, dysfunction in the subcellular retromer complex has been strongly implicated in pathogenesis of PD. Although the function and dysfunction of the retromer has been a focus of study for some time, the role of this complex in the development of PD is not fully understood. Investigating cellular alterations that occur when the retromer is rendered dysfunctional, such as when the D620N disease-causing mutation is introduced into various model systems, shows that endosomal processing defects are major contributors to the disease phenotype. Altered trafficking of retromer cargo molecules, reduced cellular survival and altered processing of alpha-synuclein have all been observed in the presence of the D620N mutation. In addition, interactions between the retromer and the protein products of other familial Parkinsonism-related genes, has made the retromer a prime target of research in PD. This review gives an overview of the changes in retromer function, identified thus far, that may contribute to the neurodegeneration observed in PD. |
| |
| Keywords: | Parkinson's disease Retromer complex VPS35 D620N mutations Trafficking |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
