Genetics of Parkinsonism: a review

Ann Hum Genet. 2001 Mar;65(Pt 2):111-26. doi: 10.1017/S0003480001008557.

Abstract

Idiopathic Parkinson's disease (IPD), a progressive neurodegenerative disorder, is a common cause of disability. No current therapies modify disease progression. The pathological hallmarks are the presence of Lewy bodies and massive loss of dopaminergic neurons in the pars compacta of the substantia nigra. Two genes (SNCA and parkin) as well as two gene loci have now been implicated in the pathogenesis of familial PD. These represent significant progress in our understanding of the disease, considering the rarity of large families, low heritability in the general population and genetic heterogeneity. Mutations in a further gene, UCHL1, have been described in familial PD although the evidence for its role in PD is less clear. Knowledge of the genes described in PD to date should help to define molecular mechanisms of neurodegeneration in PD, as well as in other diseases where defects in protein handling may be a common feature. Nigral degeneration with Lewy body formation and the resulting clinical picture of PD may represent a final common pathway of a multifactorial disease process in which both environmental and genetic factors have a role. This review discusses the major advances in the field to date and illustrates how the existence of genetic factors has now become firmly established.

Publication types

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

MeSH terms

  • Humans
  • Lewy Bodies / pathology
  • Ligases / genetics
  • Nerve Tissue Proteins / genetics
  • Parkinson Disease / etiology*
  • Parkinson Disease / genetics*
  • Substantia Nigra / pathology
  • Synucleins
  • Ubiquitin-Protein Ligases*
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Ligases