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Review
. 2011:2011:201696.
doi: 10.1155/2011/201696. Epub 2011 Sep 25.

The recent understanding of the neurotrophin's role in skeletal muscle adaptation

Kunihiro Sakuma  1 , Akihiko Yamaguchi
Affiliations
Review

The recent understanding of the neurotrophin's role in skeletal muscle adaptation

Kunihiro Sakuma et al. J Biomed Biotechnol. 2011.

Abstract

This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression). In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease.

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Figures

Figure 1
Figure 1
The interaction (preference of binding) between neurotrophins and these receptors. The low-affinity receptor p75NTR binds all neurotrophins with similar affinity but not different kinetics. Trk receptors are a family of transmembrane glycoprotein, which includes three members, TrkA, TrkB, and TrkC. The full-length TrkA, TrkB, and TrkC have estimated molecular weights of 140, 145, and 145 kDa, respectively. Each Trk preferentially binds a single neurotrophin. TrkA is the receptor for NGF, both BDNF and NT-4/5 bind to TrkB, and NT-3 is the ligand for TrkC. GDNF dimer forms a complex with GFR-α1, and this complex induces dimerization of Ret. BDNF: brain-derived neurotrophic factor, GDNF: glial cell-line derived neurotrophic factor, and NT-4/5: neurotrophin-4/5.
Figure 2
Figure 2
Schematic diagram of the functional role of skeletal muscle-derived neurotrophic factors after exercise. Exercise (neuromuscular activity) increases BDNF expression in skeletal muscle. In the patients with spinal cord injury, BDNF stimulates protein synthesis by activating Akt/mTOR/p70S6K pathway through TrkB receptor on muscle membrane. BDNF also promotes the fat oxidation through AMPK-ACC signaling. BDNF produced by skeletal muscle after exercise may circulate into brain to improve the impaired learning and/or depression. Increased GDNF protein after exercise promotes the amount of neurotransmitter (e.g., ACh) at NMJ by conjugating with Ret in presynaptic region (axon terminal). NT-4/5 may possess similar role of GDNF. BDNF: brain-derived neurotrophic factor, GDNF: glial cell-line derived neurotrophic factor, NT-4/5: neurotrophin-4/5, NMJ: neuromuscular junction, TORC1: a component of TOR signaling complex 1, Rheb: Ras homolog enriched in brain, mTOR: mammalian target of rapamycin, AMPK: AMP-activated protein kinase, and ACC: acetyl CoA carboxylase.
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