Peroxisome proliferator-activated receptor (PPAR) agonists as a potential therapy for inherited metabolic disorders.

Autor: Seminotti B; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA., Grings M; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil., Glänzel NM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil., Vockley J; Division of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA., Leipnitz G; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, CEP 90035-190, Porto Alegre, RS, Brazil; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. Electronic address: guilhian@ufrgs.br.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2023 Mar; Vol. 209, pp. 115433. Date of Electronic Publication: 2023 Jan 26.
DOI: 10.1016/j.bcp.2023.115433
Abstrakt: Inherited metabolic disorders (IMDs) are genetic disorders that cause a disruption of a specific metabolic pathway leading to biochemical, clinical and pathophysiological sequelae. While the metabolite abnormalities in body fluids and tissues can usually be defined by directed or broad-spectrum metabolomic analysis, the pathophysiology of these changes is often not obvious. Mounting evidence has revealed that secondary mitochondrial dysfunction, mainly oxidative phosphorylation impairment and elevated reactive oxygen species, plays a pivotal role in many disorders. Peroxisomal proliferator-activated receptors (PPARs) consist of a group of nuclear hormone receptors (PPARα, PPARβ/δ, and PPARγ) that regulate multiple cellular functions and processes, including response to oxidative stress, inflammation, lipid metabolism, and mitochondrial bioenergetics and biogenesis. In this context, the activation of PPARs has been shown to stimulate oxidative phosphorylation and reduce reactive species levels. Thus, pharmacological treatment with PPAR activators, such as fibrates, has gained much attention in the last 15 years. This review summarizes preclinical (animal models and patient-derived cells) and clinical data on the effect of PPARs in IMDs.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [B.S., M.G., N.M.G. and G.L. have no competing interests related to these studies. J.V. has received research funding from Reneo Pharmaceuticals, Inc. for their clinical trials on a PPAR agonist.].
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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