Neuroprotective mechanisms of chronic physical exercise via reduction of β-amyloid protein in experimental models of Alzheimer's disease: A systematic review

• Published in: Life sciences (1973) Vol. 275; p. 119372
• Main Authors: Vasconcelos-Filho, Francisco Sérgio Lopes, da Rocha Oliveira, Lucas Christyan, de Freitas, Tereza Brenda Clementino, de Pontes, Pedro Alberto Diógenes Saldanha, da Rocha-e-Silva, Roberta Cristina, Chaves, Edna Maria Camelo, da Silva, Claudio Gleidiston Lima, Soares, Paula Matias, Ceccatto, Vânia Marilande
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.06.2021; Elsevier BV
• Subjects: Alzheimer Disease - pathology; Alzheimer Disease - prevention & control; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid plaque; Animal models; Animals; Beta-amyloid protein; Bias; Brain - pathology; Dementia; Exercise; Mice; Neurodegenerative disease; Neurodegenerative diseases; Neurological complications; Neuroprotection; Physical activity; Physical Conditioning, Animal; Physical exercise; Physical fitness; Physical training; Physiological effects; Physiology; Plaque, Amyloid - pathology; Plaque, Amyloid - prevention & control; Plaque, Amyloid - therapy; Proteins; Reduction; Regular exercise; Running; Senile plaques; Swimming; Systematic review; Training; Treadmills; Wheel running; β-Amyloid; Amyloid plaque; Physical activity; Regular exercise; Neurodegenerative disease; Alzheimer's disease; Beta-amyloid protein; Dementia
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119372

Alzheimer's disease (AD) is the most common irreversible chronic neurodegenerative disease. It is characterized by the abnormal accumulation of β-amyloid protein (Aβ), which triggers homeostatic breakage in several physiological systems. However, the effect of chronic exercise on the formation of Aβ as an alternative therapy has been investigated. This systematic review examines the antiamyloid effect of different types and intensities of exercise, seeking to elucidate its neuroprotective mechanisms. The research was conducted in the electronic databases Pubmed, Embase, Scopus and Web of Science, using the following descriptors: “amyloid beta” (OR senile plaque OR amyloid plaque) and “exercise” (OR physical activity OR training). The risk of bias was evaluated through SYRCLE's Risk of Bias for experimental studies. 2268 articles were found, being 36 included in the study. A higher frequency of use of mice with genetic alterations was identified for the Alzheimer's disease (AD) model (n = 29). It was used as chronic training: treadmill running (n = 24), voluntary running wheel (n = 7), swimming (n = 4) and climbing (n = 2). The hippocampus and the cortex were the most investigated regions. However, physiological changes accompanied by the reduction of Aβ and associated with AD progression were verified. It is concluded that exercise reduces the production of Aβ in models of animals with AD. Nevertheless, this effect contributes to the improvement of several physiological aspects related to Aβ and that contribute to neurological impairment in AD. Molecular mechanism of anti-amyloidogenic effect of chronic exercise. 1) Increase of α-secretase stimulating the non-amyloidogenic pathway; 2) decrease of β-secretase reducing the amyloidogenic pathway; 3) influx and accumulation of Aβ; 4) increase of Aβ degradation by NEP and IDE, contributing to 5) Aβ reduction; decrease of: 6) inflammation, 7) cellular apoptosis, 8) phosphorylation of tau protein and 9) oxidative stress and mitophagic activity; in addition to the increase of neurogenesis and improvement of glucose and lipid metabolism. [Display omitted]