Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson's disease models.
Commun Biol
; 4(1): 232, 2021 02 19.
Article
en En
| MEDLINE
| ID: mdl-33608634
ABSTRACT
Convincing evidence supports the premise that reducing α-synuclein levels may be an effective therapy for Parkinson's disease (PD); however, there has been lack of a clinically applicable α-synuclein reducing therapeutic strategy. This study was undertaken to develop a blood-brain barrier and plasma membrane-permeable α-synuclein knockdown peptide, Tat-ßsyn-degron, that may have therapeutic potential. The peptide effectively reduced the level of α-synuclein via proteasomal degradation both in cell cultures and in animals. Tat-ßsyn-degron decreased α-synuclein aggregates and microglial activation in an α-synuclein pre-formed fibril model of spreading synucleinopathy in transgenic mice overexpressing human A53T α-synuclein. Moreover, Tat-ßsyn-degron reduced α-synuclein levels and significantly decreased the parkinsonian toxin-induced neuronal damage and motor impairment in a mouse toxicity model of PD. These results show the promising efficacy of Tat-ßsyn-degron in two different animal models of PD and suggest its potential use as an effective PD therapeutic that directly targets the disease-causing process.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Péptidos
/
Encéfalo
/
Intoxicación por MPTP
/
Alfa-Sinucleína
/
Neuronas
/
Antiparkinsonianos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Commun Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá