Affiliations: [a] School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| [b] Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| [c] Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| [d] Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro, Brazil
| [e] Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada
Correspondence:
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Correspondence to: Dr. Mychael V. Lourenco, Institute of Medical Biochemistry Leopoldo de Meis and Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil. Tel.: +55 21 3938 6579; E-mail: mychael@bioqmed.ufrj.br.
Note: [1] These authors contributed equally to this work.
Abstract: Clinical trials have extensively failed to find effective treatments for Alzheimer’s disease (AD) so far. Even after decades of AD research, there are still limited options for treating dementia. Mounting evidence has indicated that AD patients develop central and peripheral metabolic dysfunction, and the underpinnings of such events have recently begun to emerge. Basic and preclinical studies have unveiled key pathophysiological mechanisms that include aberrant brain stress signaling, inflammation, and impaired insulin sensitivity. These findings are in accordance with clinical and neuropathological data suggesting that AD patients undergo central and peripheral metabolic deregulation. Here, we review recent basic and clinical findings indicating that metabolic defects are central to AD pathophysiology. We further propose a view for future therapeutics that incorporates metabolic defects as a core feature of AD pathogenesis. This approach could improve disease understanding and therapy development through drug repurposing and/or identification of novel metabolic targets.
