Early metabolic impairment as a contributor to neurodegenerative disease: Mechanisms and potential pharmacological intervention.

Autor: Fakih W; Faculty of Pharmacy, Federation of Translational Medicine of Strasbourg, University of Strasbourg, Illkirch, France.; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon., Zeitoun R; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon., AlZaim I; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon., Eid AH; Department of Basic Medical Sciences, College of Medicine, Qatar University, Doha, Qatar.; Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar., Kobeissy F; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.; Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, Florida, USA., Abd-Elrahman KS; Brain and Mind Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.; Department of Pharmacology and Therapeutics, College of Medicine and Health Science, Khalifa University, Abu Dhabi, United Arab Emirates., El-Yazbi AF; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alamein International University, New Alamein City, Egypt.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2022 May; Vol. 30 (5), pp. 982-993.
DOI: 10.1002/oby.23400
Abstrakt: The metabolic syndrome comprises a family of clinical and laboratory findings, including insulin resistance, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hypertension, in addition to central obesity. The syndrome confers a high risk of cardiovascular mortality. Indeed, metabolic dysfunction has been shown to cause a direct insult to smooth muscle and endothelial components of the vasculature, which leads to vascular dysfunction and hyperreactivity. This, in turn, causes cerebral vasoconstriction and hypoperfusion, eventually contributing to cognitive deficits. Moreover, the metabolic syndrome disrupts key homeostatic processes in the brain, including apoptosis, autophagy, and neurogenesis. Impairment of such processes in the context of metabolic dysfunction has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington diseases. The aim of this review is to elucidate the role that the metabolic syndrome plays in the pathogenesis of the latter disorders, with a focus on the role of perivascular adipose inflammation in the peripheral-to-central transduction of the inflammatory insult. This review delineates common signaling pathways that contribute to these pathologies. Moreover, the role of therapeutic agents aimed at treating the metabolic syndrome, as well as their risk factors that interfere with the aforementioned pathways, are discussed as potential interventions for neurodegenerative diseases.
(© 2022 The Obesity Society.)
Databáze: MEDLINE
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