Activation of the muscle‐to‐brain‐axis reduces amyloid plaque accumulation and rescues behavioral deficits by enhancing synaptic integrity and neurotrophic signaling in a mouse model of Alzheimer’s disease.
Abstract
Alzheimer’s disease (AD) is associated with complex pathophysiology including synaptic dysregulation, compromised neurotrophic signaling, deficits in autophagic flux and neuroinflammation). Skeletal muscle regulates many brain functions relevant to aging, by activating the muscle‐to‐brain axis through the secretion of skeletal muscle originating factors (myokines) with cellular‐modifying, neuro and geroprotective properties. Our group developed transgenic mice that overexpress the skeletal muscle human Transcription Factor EB (TFEB), a master regulator of lysosomal‐to‐nucleus signaling, resulting in enhanced proteostasis and neuroprotection in a Tau mouse model. However, the precise mechanisms remain unknown. Therefore, we further validated these effects in an AD amyloid β (Aβ) mouse model and investigated the underlying mechanism.
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Research summary
The paper investigates the activation of the muscle-to-brain axis and its effects on amyloid plaque accumulation and behavioral deficits in a mouse model of Alzheimer's disease. This research touches on mechanisms that could potentially address underlying issues related to aging and neurodegeneration, which are relevant to longevity research. However, the focus remains primarily on a specific disease model rather than directly targeting the root causes of aging itself. The findings contribute solidly to the understanding of neuroprotection and synaptic integrity but do not represent a major breakthrough or transformative advance in the field of longevity research.
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