Synucleinopathies: clinical and pathological implications

Arch Neurol. 2001 Feb;58(2):186-90. doi: 10.1001/archneur.58.2.186.


The synucleinopathies are a diverse group of neurodegenerative disorders that share a common pathologic lesion composed of aggregates of insoluble alpha-synuclein protein in selectively vulnerable populations of neurons and glia. Growing evidence links the formation of abnormal filamentous aggregates to the onset and progression of clinical symptoms and the degeneration of affected brain regions in neurodegenerative disorders. These disorders may share an enigmatic symmetry, i.e., missense mutations in the gene encoding for the disease protein (alpha-synuclein) cause familial variants of Parkinson disease as well as its hallmark brain lesions, but the same brain lesions also form from the corresponding wild-type brain protein in the more common sporadic varieties of Parkinson disease. It is likely that clarification of this enigmatic symmetry in 1 form of synucleinopathy will have a profound impact on understanding the mechanisms underlying all these disorders. Furthermore, these efforts will likely lead to novel diagnostic and therapeutic strategies in regard to the synucleinopathies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Lewy Body Disease / genetics
  • Lewy Body Disease / metabolism
  • Lewy Body Disease / physiopathology
  • Multiple System Atrophy / genetics
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / physiopathology
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / physiopathology
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Synucleins
  • alpha-Synuclein


  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein