Oligodendrocytes from neural stem cells express α-synuclein:: increased numbers from presenilin I deficient mice

alpha-Synuclein normally a synaptic vesicle-associated cytoplasmic protein is the major component of filamentous inclusions of neurons in Parkinson's disease and dementia with Lewy bodies. It is also the major component of glial inclusions of multiple system atrophy. In characterizing cells derived from embryonic neural stem cells we found all oligodendrocytes had strong cytoplasmic expression of alpha-synuclein. Comparison of cells from presenilin I (PSI)-deficient mice with wild type revealed a 7-fold increase in oligodendrocytes. Western blotting analysis indicated the cells contained alpha-synuclein monomers and SIDS-stable dinners and trimers, This cell system of oligodendroglial alpha-synuclein expression is a useful system to study alpha-synuclein metabolism in the cell type affected in multiple system atrophy. Increased oligodendroglial cell numbers from PSI-deficient cells provides further evidence for a role of PSI-dependent Notch signalling in cell fate decisions.