Alpha-synuclein and beta-amyloid - different targets, same players: calcium, free radicals and mitochondria in the mechanism of neurodegeneration.
Biochem Biophys Res Commun
; 483(4): 1110-1115, 2017 02 19.
Article
em En
| MEDLINE
| ID: mdl-27470584
ABSTRACT
Two of the most devastating neurodegenerative diseases are consequences out of misfolding and aggregation of key proteins-alpha synuclein and beta-amyloid. Although the primary targets for the two proteins are different, they both share a common mechanism that involves formation of pore-like structure on the plasma membrane, consequent dysregulation of calcium homeostasis, mitochondrial dysfunction and oxidative damage. The combined effect of all this factors ultimately leads to neuronal cell death. Whereas beta amyloid acts on the astrocytic plasma membrane, exhibiting a tight dependence to the membrane cholesterol content, alpha-synuclein does not distinguish between type of membrane or cell. Additionally, oligomeric forms of both proteins produce reactive oxygen species through different mechanisms beta-amyloid through activation of the NADPH oxidase and alpha-synuclein through non-enzymatic way. Finally, both peptides in oligomeric form induce mitochondrial depolarisation through calcium overload and free radical production that ultimately lead to opening of the mitochondrial permeability transition pore and trigger cell death.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Peptídeos beta-Amiloides
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Alfa-Sinucleína
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2017
Tipo de documento:
Article