Soluble mediators secreted by skeletal muscles (collectively referred to as myokines) exert systemic effects by signaling to distant organs. Rai et al. have now uncovered a muscle-to-central nervous system (CNS) signaling axis, which is engaged in response to proteostatic stress. These adaptations confer protection against pathological protein accumulation in the CNS, a hallmark of neurodegenerative diseases.
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