The genetics of disorders with synuclein pathology and parkinsonism

Hum Mol Genet. 1999;8(10):1901-5. doi: 10.1093/hmg/8.10.1901.

Abstract

Despite being considered the archetypal non-genetic neurological disorder, genetic analysis of Parkinson's disease has shown that there are at least three genetic loci. Furthermore, these analyses have suggested that the phenotype of the pathogenic loci is wider than simple Parkinson's disease and may include Lewy body dementia and some forms of essential tremor. Identification of alpha-synuclein as the first of the loci involved in Parkinson's disease and the identification of this protein in pathological deposits in other disorders has led to the suggestion that it may share pathogenic mechanisms with multiple system atrophy, Alzheimer's disease and prion disease and that these mechanisms are related to a synuclein pathway to cell death. Finally, genetic analysis of the synuclein diseases and the tau diseases may indicate that this synuclein pathway is an alternative to the tau pathway to cell death.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Humans
  • Multiple System Atrophy / genetics
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / pathology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Parkinsonian Disorders / genetics*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology*
  • Supranuclear Palsy, Progressive / genetics
  • Supranuclear Palsy, Progressive / metabolism
  • Supranuclear Palsy, Progressive / pathology
  • Synucleins
  • alpha-Synuclein
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

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