Abstract
Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer’s disease, or the most common neurodegenerative motor disorder, Parkinson’s disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle–brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players. Here, we provide an overview on the central role of mitochondria in exercise-induced communication routes from muscle to the brain. These routes include circulating factors, such as myokines, the release of which often depends on mitochondria, and possibly direct mitochondrial transfer. On this basis, we examine the reported effects of different modes of exercise on mitochondrial features and highlight their expected benefits with regard to neurodegeneration prevention or mitigation. In addition, knowledge gaps in our current understanding related to the muscle–brain axis in neurodegenerative diseases are outlined.
Highlights
The umbrella term “neurodegenerative disease” refers to the progressive pathological loss of neurons in specific neuronal circuits
We focus on the muscle–brain crosstalk mediated by mitochondria for the beneficial effect of exercise in AD and Parkinson’s diseases (PD)
Irisin is an exercise-induced myokine released by the cleavage of the membranebound precursor protein fibronectin type III domain-containing protein 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of PGC-1α [136]
Summary
The umbrella term “neurodegenerative disease” refers to the progressive pathological loss of neurons in specific neuronal circuits. AD and PD are the most common causes of dementia and of neurodegenerative motor diseases, respectively. Their global prevalence has been estimated to be about. Notably including physical activity and exercise, are major factors in modulating the risk of developing these neurodegenerative diseases [5,6,7]. Regular endurance exercise improves cardiorespiratory fitness and skeletal muscle function and has well-documented health effects, including reduced all-cause mortality [9]. It importantly influences mitochondrial health [10,11]. The convergence of pathogenic mechanisms in many neurodegenerative diseases that include mitochondrial dysfunction and oxidative stress [12,13], protein aggregation [14,15], inflammation [16], and brain regional vulnerabilities [17] highlight the relevance of the related influences of muscle–brain crosstalk for other neurodegenerative diseases
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