Synucleinopathies - Clinical and pathological implications

The synucleinopathies are a diverse group of neurodegenerative disorders th at share a common pathologic lesion composed of aggregates of insoluble alp ha -synuclein protein in selectively vulnerable populations of neurons and glia. Growing evidence links the formation of abnormal filamentous aggregat es to the onset and progression of clinical symptoms and the degeneration o f affected brain regions in neurodegenerative disorders. These disorders ma y share an enigmatic symmetry, ie, missense mutations in the gene encoding for the disease protein (alpha -synuclein) cause familial variants of Parki nson disease as well as its hallmark brain lesions, but the same brain lesi ons also form from the corresponding wild-type brain protein in the more co mmon sporadic varieties of Parkinson disease. It is likely that clarificati on of this enigmatic symmetry in 1 form of synucleinopathy will have a prof ound impact on understanding the mechanisms underlying all these disorders. Furthermore, these efforts will likely lead to novel diagnostic and therap eutic strategies in regard to the synucleinopathies.