Muscle-Brain crosstalk in cognitive impairment

Abstract

Sarcopenia is an age-related, involuntary loss of skeletal muscle mass and strength. Alzheimer's disease (AD) is the most common cause of dementia in elderly adults. To date, no effective cures for sarcopenia and AD are available. Physical and cognitive impairments are two major causes of disability in the elderly population, which severely decrease their quality of life and increase their economic burden. Clinically, sarcopenia is strongly associated with AD. However, the underlying factors for this association remain unknown. Mechanistic studies on muscle-brain crosstalk during cognitive impairment might shed light on new insights and novel therapeutic approaches for combating cognitive decline and AD. In this review, we summarize the latest studies emphasizing the association between sarcopenia and cognitive impairment. The underlying mechanisms involved in muscle-brain crosstalk and the potential implications of such crosstalk are discussed. Finally, future directions for drug development to improve age-related cognitive impairment and AD-related cognitive dysfunction are also explored.

Keywords: Alzheimer's disease; aging; cognitive impairment; sarcopenia; skeletal muscle.

Figure 1

Muscle–brain crosstalk in cognitive dysfunction. Myokines or cytokines released from skeletal muscle affect neurons and inflammation in the brain: (1) detrimental factors: cathepsin B, myostatin, and GDF-15; (2) dual roles: IL-15, IL-6, LIF, and lactate; (3) beneficial factors: FNDC5, BDNF, IGF-1, and SPARC. Exercise-enhancing release of beneficial factors and specific overexpression of neprilysin and scFv59 in the skeletal muscle could be promising strategies against cognitive dysfunction. GDF15, Growth differentiation factor-15; IL-8, interleukin 8; IL-15, interleukin-15; IL-6, interleukin-6; LIF, leukemia inhibitory factor; FNDC5, fibronectin type III domain containing protein 5; BDNF, brain-derived neurotrophic factor; IGF-1, insulin-like growth factor-1; SPARC, secreted protein acidic and rich in cysteine.