Enhancing CNS mitophagy: drug development and disease-relevant models.

Autor: Dhar KS; School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia., Townsend B; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Montgomery AP; School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia., Danon JJ; School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia., Pagan JK; Faculty of Medicine, School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia., Kassiou M; School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: michael.kassiou@sydney.edu.au.
Jazyk: angličtina
Zdroj: Trends in pharmacological sciences [Trends Pharmacol Sci] 2024 Nov; Vol. 45 (11), pp. 982-996. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.tips.2024.09.002
Abstrakt: Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs. We also highlight the complexities of mitophagy in the CNS, highlighting the need for disease-relevant models. Last, we outline crucial aspects of in vitro models to consider during drug discovery, aiming to bridge the gap between preclinical research and clinical applications in treating NDs through mitophagy modulation.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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