Lysosomal response in relation to α-synuclein pathology differs between Parkinson's disease and multiple system atrophy.

摘要: Abstract Intracellular deposition of pathologically altered α-synuclein mostly in neurons characterises Parkinson's disease (PD), while its accumulation predominantly oligodendrocytes is a feature multiple system atrophy (MSA). Recently prion-like spreading pathologic has been suggested to play role the pathogenesis PD and MSA. This implicates protein processing systems, including lysosomes, supported also by genetic studies PD. However, particularly for MSA, mechanism cell-to-cell propagation yet not fully understood. To evaluate significance lysosomal response, we systematically compared differently affected neuronal populations PD, non-diseased brains using morphometric immunohistochemistry (cathepsin D), double immunolabelling D/α-synuclein) laser confocal microscopy, immunogold electron microscopy associated α-synuclein. We found that i) irrespective presence inclusions, volume density cathepsin D immunoreactivity significantly increases pontine base MSA brains; ii) nigral without inclusions with non-ubiquitinated pre-aggregates α-synuclein, but Lewy bodies; iii) frequently colocalises PD; iv) ultrastructural observations confirm disease-associated astrocytic lysosomes v) lysosome-associated observed astroglia rarely oligodendroglia Our support crucial endosomal-lysosomal suggest distinct contribution possibility oligodendroglial eventually uptake exogenous