Role of Oligomeric a-Synuclein in Mitochondrial Membrane Permeabilization and Neurodegeneration in Parkinson's Disease
Abstract
A growing body of evidence suggests that aggregation of alpha-syn might be the fundamental cause of many neurodegenerative diseases. Several groups have developed cell culture models to study the cytotoxic effect of alpha-synuclein, and some of them indeed have observed enhanced cell death when alpha-syn, especially its mutant forms, was overexpressed. However, the link between alpha-syn aggregation and cell death has not been clearly addressed in these model systems, nor are the molecular mechanisms underlying the toxicity known. We have begun to address these issues in a COS-7 cell model, and found that alpha-syn aggregation/oligomerization is tightly associated with Golgi fragmentation and cell death. The fragmentation of the GA has been also confirmed in a neuronal cell model, and the mode of Golgi fragmentation appears identical to that caused by microtubule-disrupting agents; dispersed Golgi fragments are localized to the transitional endoplasmic reticulum. These findings indicate that alpha-syn aggregation leads to impairment of microtubule-dependent intracellular trafficking, which in turn causes Golgi fragmentation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA421068
Entities
People
- Sueng-jae Lee