Article Abstract

Effect of mammalian target of rapamycin signaling pathway on nerve regeneration

Authors: Ziwei Huang, Jianwei Zhu, Jiacheng Sun, Wenjing Ma, Lingbin Wang, Qiuyu Zhang, Hualin Sun

Abstract

Nerve injury is a serious clinical common problem not only caused by violence usually in traffic accident but also non-violence related disease like amyotrophic lateral sclerosis and other motor neuron diseases. All these diseases always come with severe consequences including loss of function and even to paralysis which are associated with significant high mortality. Although many useful treatments have been developed, completely recovery of damaged nerve function is usually hardly obtained. Because successful functional recovery of injured nerve lie in not only axon regeneration, neuronal survival but also reconstructing transmission of myelin-based electric nerve stimulation as well as re-innervation of denervated targets. Recent research has suggested that low intrinsic capacity of neuron may be genuinely responsible for regeneration failure. PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway has been found playing crucial roles in the growth of central nervous system axons, and confirmed as a major intracellular signaling axis that control axon regeneration. In nerve dissection animal models, the mTOR activity was suppressed and protein synthesis was impaired, while reactivating this pathway successfully led to axon regeneration. Emerging evidence show that mTOR is required during multiple intricate physiological process in nerve regeneration. This review focuses on recent study which are mTOR related, introducing basic knowledge of mTOR including protein structure and its function in either physiological or pathological process, discussing the therapeutic potential of mTOR-based treatment.