Lewy-body Formation Is an Aggresome-Related Process: A Hypothesis

Lancet Neurol. 2004 Aug;3(8):496-503. doi: 10.1016/S1474-4422(04)00827-0.

Abstract

Parkinson's disease (PD) is an age-related neurodegenerative disorder that is associated with the formation of intracytoplasmic protein aggregates (Lewy-body inclusions) in neurons of the substantia nigra pars compacta and other brain areas. These inclusions were discovered over 90 years ago, but the mechanism underlying their formation and their relevance to the neurodegenerative process are unknown. Recent studies have begun to shed light on the biogenesis of Lewy bodies and suggest that they are related to aggresomes. Aggresomes are cytoprotective proteinaceous inclusions formed at the centrosome that segregate and facilitate the degradation of excess amounts of unwanted and possibly cytotoxic proteins. The concept of Lewy bodies as aggresome-related inclusions fits well with ongoing discoveries suggesting that altered protein handling might contribute to the neurodegenerative process in familial and sporadic forms of PD.

Publication types

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

MeSH terms

  • Dopamine / metabolism
  • Humans
  • Inclusion Bodies / metabolism*
  • Inclusion Bodies / pathology
  • Lewy Bodies / metabolism*
  • Models, Biological
  • Nerve Tissue Proteins / metabolism
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology
  • Synucleins
  • Tubulin / metabolism
  • Ubiquitin / metabolism

Substances

  • Nerve Tissue Proteins
  • Synucleins
  • Tubulin
  • Ubiquitin
  • Dopamine