Autophagy-targeted therapy to modulate age-related diseases: Success, pitfalls, and new directions.

Autor:	Martins WK; Laboratory of Cell and Membrane (LCM), Anhanguera University of São Paulo (UNIAN), Rua Raimundo Pereira de Magalhães, 3,305. Pirituba, São Paulo, 05145-200, Brazil., Silva MDND; Laboratory of Cell and Membrane (LCM), Anhanguera University of São Paulo (UNIAN), Rua Raimundo Pereira de Magalhães, 3,305. Pirituba, São Paulo, 05145-200, Brazil., Pandey K; Center for Neural Science, New York University, Meyer Building, Room 823, 4 Washington Place, New York, NY, 10003, USA., Maejima I; Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa Machi, Maebashi, Gunma, 3718512, Japan., Ramalho E; Laboratory of Cell and Membrane (LCM), Anhanguera University of São Paulo (UNIAN), Rua Raimundo Pereira de Magalhães, 3,305. Pirituba, São Paulo, 05145-200, Brazil., Olivon VC; Laboratory of Pharmacology and Physiology, UNIDERP, Av. Ceará, 333. Vila Miguel Couto, Campo Grande, MS, 79003-010, Brazil., Diniz SN; Laboratory of Molecular Biology and Functional Genomics, Anhanguera University of São Paulo (UNIAN), Rua Raimundo Pereira de Magalhães, 3,305. Pirituba, São Paulo, 05145-200, Brazil., Grasso D; Instituto de Estudios de la Inmunidad Humoral (IDEHU), Universidad de Buenos Aires, CONICET, Junín 954 p4, Buenos Aires, C1113AAD, Argentina.
Jazyk:	angličtina
Zdroj:	Current research in pharmacology and drug discovery [Curr Res Pharmacol Drug Discov] 2021 Jun 01; Vol. 2, pp. 100033. Date of Electronic Publication: 2021 Jun 01 (Print Publication: 2021).
DOI:	10.1016/j.crphar.2021.100033
Abstrakt:	Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field. Competing Interests: 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. (© 2021 The Author(s).)
Databáze:	MEDLINE
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