Skeletal muscle health is inseparable from brain health

📖 Literature Information and Abstract Translation

Integrative physiology of skeletal muscle for maintaining cognitive health

[Review Summary] This review outlines the importance of skeletal muscle in cognitive function and discusses the possibility that the health status of skeletal muscle and peripheral motor nerves could serve as new indicators for Alzheimer's disease risk.

① Skeletal muscle → Brain: Maintenance of cognitive function via myokines

　　　　　 Muscle contraction/exercise
　　　　　　　　↓
　　Release of myokines from skeletal muscle
　　　　　　　　↓
　　Acts on the brain via the blood
　　　　　　　　↓
　Increases Brain-Derived Neurotrophic Factor (BDNF), etc.
　　　　　　　　↓
　　Promotes neurogenesis and neuroplasticity
　　　　　　　　↓
　　　　　Maintains cognitive function

Representative factors include irisin, Cathepsin B, and pro-saposin (PSAP).
Skeletal muscle is not just a locomotor organ, but also an "endocrine organ" that acts on the brain.

② Brain → Motor nerves → Skeletal muscle: Maintenance of the neuromuscular system

In Alzheimer's disease, abnormalities may also occur in peripheral motor nerves and neuromuscular junctions.
The decline in neuromuscular function may appear earlier than cognitive decline and could serve as an early indicator of Alzheimer's disease.

③ Alzheimer's disease-related changes are not "just in the brain"

The figure depicts amyloid precursor protein (APP) and amyloid β (Aβ) not only in the brain but also in skeletal muscle.
Amyloid precursor protein (APP) is also present at the neuromuscular junction, and its abnormality may affect neuro-muscular signal transmission.
It is important to view Alzheimer's disease not as a "disease of the brain alone," but as a systemic change involving peripheral nerves and skeletal muscle.

④ Mitochondrial function is also a key element connecting the brain and muscles

Since both skeletal muscle and nerves require large amounts of energy, mitochondrial function is crucial.
In particular, it has been reported that decreased mitochondrial function in skeletal muscle is associated with future cognitive impairment and Alzheimer's disease-related biomarkers.
The energy metabolic state of skeletal muscle may reflect the health status of the brain.

⑤ AMPK: An energy sensor with different roles in the brain and muscles

AMP-activated protein kinase (AMPK) senses the energy state of cells and regulates mitochondrial function, among other things.
The figure specifically shows:
・AMP-activated protein kinase α1 (AMPKα1)
・AMP-activated protein kinase α2 (AMPKα2)
While the action of AMPK in skeletal muscle is important for maintaining muscles, mitochondria, and neuromuscular junctions, excessive AMPK activity in the Alzheimer's brain may be related to the pathology.
Because the action of AMPK differs depending on the tissue, it is not a simple matter of "just increasing AMPK throughout the body."

🌱 So What?: What did I find interesting?

Exercise maintains and improves cognitive function.
"Exercise is Medicine" is one of its representative effects.
I have read several related papers (see related notes).

What exactly is the mechanism behind this?
This study illustrated the mechanism at a micro level.
A new personal discovery was that abnormalities can occur in peripheral motor nerves and neuromuscular junctions, and that amyloid precursor protein (APP) is also present at the neuromuscular junction.
I felt this specifically highlights the necessity of viewing it as a systemic disease, not just a brain problem.
Skeletal muscle and the brain.
Rather than being separate and isolated, it seems necessary to have a perspective that they are one whole entity.

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