Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity.
Life Sci Alliance
; 2(5)2019 10.
Article
en En
| MEDLINE
| ID: mdl-31533964
ABSTRACT
The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson's disease. Here, we demonstrate that polyP is unable to accelerate the rate-limiting step of α-synuclein fibril formation but effectively nucleates fibril assembly once α-synuclein oligomers are formed. Binding of polyP to α-synuclein either during fibril formation or upon fibril maturation substantially alters fibril morphology and effectively reduces the ability of α-synuclein fibrils to interact with cell membranes. The effect of polyP appears to be α-synuclein fibril specific and successfully prevents the uptake of fibrils into neuronal cells. These results suggest that altering the polyP levels in the extracellular space might be a potential therapeutic strategy to prevent the spreading of the disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polifosfatos
/
Alfa-Sinucleína
Límite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania