Physical exercise as a non-pharmacological strategy in the prevention and treatment of Alzheimer's Disease

Abstract

The number of people with Dementia is increasing substantially around the world, having a global cost similar to GDP of countries like Netherlands. Brazil occupies the ninth place in this ranking. Alzheimer Disease (AD) is the most prevalent among the neurodegenerative diseases (Dementias), having the formation of ²-amiloide plaques in the brain tissue as a characteristic. One of the factors involved in the ²-amiloide malformation and aggregation is the impairment in the autophagic-lysosomal pathway, decreasing ²-amiloide removal, allowing its aggregation, leading to neurodegeneration. Since its discovery, TFEB has demonstrated a fundamental role in the autophagic-lysosomal pathway. TFEB is the major autophagic coordinator, positively regulating lysosomal biogenesis and autolysosome formation, having the capability to ameliorate the pathological condition in neurodegenerative disease. Physical exercise is an effective approach to prevent neurodegeneration, however, the mechanisms of protection need better elucidation. Physical exercise was capable to improve neural autophagy and decrease neurodegeneration through TFEB, and in skeletal muscle through Calcineurin-TFEB pathway activation, induce autophagy. Furthermore, physical exercise was capable to induce mitochondrial biogenesis, and improve its function in skeletal muscle in a TFEB dependent manner. It is known that mitochondrial disfunctions and neurodegenerative disease have a close correlation, and mitochondrial autophagy has an important role in this condition. Therefore, the main objective of the present study is to verify if TFEB, through the autophagic-lysosomal and mitochondrial biogenesis pathways, along with Calcineurin, would be exerting its neuroprotector effect induced by the physical exercise. Mice will be divided into 4 groups: control (CT; sedentary), trained (TR; submitted to exercise protocol), sedentary AD (SAD; APP/PS1 sedentary), trained AD (TAD; APP/PS1 submitted to exercise protocol). The methods include: immunoblotting, Real-time PCR, immunofluorenscense and brain imaging. Level of significance of p<0.05 will be adopted. (AU)