[Alpha-synucleinopathies].
The term alpha-synucleinopathy is used to name a group of disorders having in common the abnormal deposition of alpha-synuclein in the cytoplasm of neurons or glial cells, as well as in extracellular deposits of amyloid. In Parkinson's disease and Lewy body dementia, alpha-synuclein is the main component of Lewy bodies and dystrophic neurites; alpha-synuclein also accumulates in the cytoplasm of glial cells. In multiple system atrophy, alpha-synuclein conforms the cytoplasmic oligodendroglial inclusions and the neuronal inclusions which are the hallmark of this disease. Finally, the amyloidogenic fragment 61-95 amino acids of alpha-synuclein is the non-Abeta component of senile plaque amyloid in Alzheimer disease. Accumulations of alpha-synuclein in all these disorders have in common a fibrilar configuration, but they differ in the binding of alpha-synuclein to distinct proteins with the exception of ubiquitin whose binding to alpha-synuclein is common to all alpha-synuclein inclusions. The mechanisms leading to alpha-synuclein fragmentation and aggegation into extracellular amyloid are not known, although alpha-synuclein fragment and betaA4 aggregates are the result of abnormal cleavage of large precursors. On the other hand, several studies have shown that alpha-synuclein may adopt a fibrilar conformation and give rise to insoluble forms and high molecular weight aggregates in vitro. Similar complexes have also been observed in alpha-synucleinopathies. Although studies in vitro and in vivo have shown toxic effects of alpha-synuclein, the consequence of alpha-synuclein deposition on cell survival in alpha-synucleinopathies is not known.
Ferrer
I
I
Unidad de Neuropatología, Servicio de Anatomía Patológica, Hospital Príncipes de España, Departamento de Biología Celular y Anatomía Patológica, Universidad de Barcelona, Spain. iferrer@sakma.es
D000544:Alzheimer Disease / Q000209:etiology; D016923:Cell Death; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000209:etiology; D019578:Multiple System Atrophy / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000209:etiology*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000209:etiology; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein