Systemic administration of a novel Beclin 1-derived peptide significantly upregulates autophagy in the spinal motor neurons of autophagy reporter mice.

Autor: Amin A; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia., Perera ND; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia., Tomas D; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia., Cuic B; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia., Radwan M; Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville 3010, VIC, Australia., Hatters DM; Department of Biochemistry and Pharmacology and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville 3010, VIC, Australia., Turner BJ; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia., Shabanpoor F; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville 3010, VIC, Australia; School of Chemistry, University of Melbourne, VIC 3010, Australia. Electronic address: fazel.shabanpoor@unimelb.edu.au.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jun 25; Vol. 659, pp. 124198. Date of Electronic Publication: 2024 May 29.
DOI: 10.1016/j.ijpharm.2024.124198
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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