Advancing Alzheimer’s Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients
Author:
Andrade-Guerrero Jesús12ORCID, Rodríguez-Arellano Paola2, Barron-Leon Nayeli2, Orta-Salazar Erika2, Ledesma-Alonso Carlos2, Díaz-Cintra Sofía2, Soto-Rojas Luis O.13ORCID
Affiliation:
1. Laboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico 2. Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Queretaro 76230, Mexico 3. Red MEDICI, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
Abstract
Alzheimer’s disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aβ) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aβ aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise’s potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.
Funder
UNAM-PAPIIT Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT), Ciencia Básica y/o Ciencia de Frontera Modalidad: Paradigmas y Controversias de la Ciencia 2022
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