Lewy-body formation is an aggresome-related process: a hypothesis.
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.
Olanow
C Warren
CW
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. warren.olanow@mssm.edu
Perl
Daniel P
DP
DeMartino
George N
GN
McNaught
Kevin St P
KS
D004298:Dopamine / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D016631:Lewy Bodies / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D051843:Synucleins; D014404:Tubulin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D051843:Synucleins; D014404:Tubulin; D025801:Ubiquitin; D004298:Dopamine