Systemic administration of a novel Beclin 1-derived peptide significantly upregulates autophagy in the spinal motor neurons of autophagy reporter mice.
Int J Pharm
; 659: 124198, 2024 Jun 25.
Article
en En
| MEDLINE
| ID: mdl-38816263
ABSTRACT
Autophagy, an intracellular degradation system, plays a vital role in protecting cells by clearing damaged organelles, pathogens, and protein aggregates. Autophagy upregulation through pharmacological interventions has gained significant attention as a potential therapeutic avenue for proteinopathies. Here, we report the development of an autophagy-inducing peptide (BCN4) derived from the Beclin 1 protein, the master regulator of autophagy. To deliver the BCN4 into cells and the central nervous system (CNS), it was conjugated to our previously developed cell and blood-brain barrier-penetrating peptide (CPP). CPP-BCN4 significantly upregulated autophagy and reduced protein aggregates in motor neuron (MN)-like cells. Moreover, its systemic administration in a reporter mouse model of autophagy resulted in a significant increase in autophagy activity in the spinal MNs. Therefore, this novel autophagy-inducing peptide with a demonstrated ability to upregulate autophagy in the CNS has significant potential for the treatment of various neurodegenerative diseases with protein aggregates as a characteristic feature.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
/
Regulación hacia Arriba
/
Beclina-1
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Neuronas Motoras
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia