skip to main content
Idioma:
Primo Search
Clear Search Box
Search in: Busca Geral
Busca Avançada
Busca por Índices

The contribution of alpha synuclein to neuronal survival and function – Implications for Parkinson's disease

Benskey, Matthew J. ; Perez, Ruth G. ; Manfredsson, Fredric P.

Journal of neurochemistry, 2016-05, Vol.137 (3), p.331-359 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

Texto completo disponível

Citações Citado por
  • Título:
    The contribution of alpha synuclein to neuronal survival and function – Implications for Parkinson's disease
  • Autor: Benskey, Matthew J. ; Perez, Ruth G. ; Manfredsson, Fredric P.
  • Assuntos: alpha-Synuclein - drug effects ; alpha-Synuclein - genetics ; alpha-Synuclein - metabolism ; alpha‐synuclein ; Animals ; Antiparkinson Agents - pharmacology ; dopamine ; Humans ; Lewy body ; Neurochemistry ; Neurons - drug effects ; Neurons - pathology ; Parkinson Disease - drug therapy ; Parkinson Disease - genetics ; Parkinson Disease - pathology ; Parkinson's disease ; Review ; substantia nigra ; synucleinopathy
  • É parte de: Journal of neurochemistry, 2016-05, Vol.137 (3), p.331-359
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Work was completed in Grand Rapids MI, USA.
  • Descrição: The aggregation of alpha synuclein (α‐syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α‐syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α‐syn gene result in familial PD. The high correlation between α‐syn burden and PD has led to the hypothesis that α‐syn aggregation produces toxicity through a gain‐of‐function mechanism. However, α‐syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α‐syn results in toxicity because of a toxic loss of necessary α‐syn function, following sequestration of functional forms α‐syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α‐syn to PD and the knowledge gained from current α‐syn‐based animal models of PD. We will then interpret these data from the viewpoint of the α‐syn loss‐of‐function hypothesis and provide a potential mechanistic model by which loss of α‐syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between α‐synuclein burden and Parkinson's disease pathology has led to the hypothesis that α‐synuclein aggregation produces toxicity through a gain‐of‐function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α‐synuclein results in toxicity because of loss of necessary α‐synuclein function at the presynaptic terminal, following sequestration of functional forms of α‐synuclein into aggregates. The correlation between α‐synuclein burden and Parkinson's disease pathology has led to the hypothesis that α‐synuclein aggregation produces toxicity through a gain‐of‐function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α‐synuclein results in toxicity because of loss of necessary α‐synuclein function at the presynaptic terminal, following sequestration of functional forms of α‐synuclein into aggregates.
  • Editor: England: Blackwell Publishing Ltd
  • Idioma: Inglês
Links
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.