Cytoskeleton dysfunction of motor neuron in spinal muscular atrophy
T.-J. Shi, Zijie Zhou, Taiyang Xiang, Yinxuan Suo, Xiaoyan Shi, Yaoyao Li, Peng Zhang, Jun Yan Dai, Lei Sheng
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deletions or mutations of survival of motor neuron 1 (SMN1) gene. To date, the mechanism of selective cell death of motor neurons as a hallmark of SMA is still unclear. The severity of SMA is dependent on the amount of survival motor neuron (SMN) protein, which is an essential and ubiquitously expressed protein involved in various cellular processes including regulation of cytoskeletal dynamics. In this review, we discuss the effect of SMN ablation on cytoskeleton organization including actin dynamics, growth cone formation, axonal stability, neurite outgrowth, microtubule stability, synaptic vesicle dynamics and neurofilament protein release in SMA. We also summarized a list of critical proteins such as profilin-2 (PFN2), plastin-3 (PLS3), stathmin-1 (STMN1), microtubule-associated protein 1B (MAP1B) and neurofilament which play an important role in modulating cytoskeleton in SMA. Our aim is to highlight how cytoskeletal defects contribute to motor neuron degeneration in SMA disease progression and concentrating on cytoskeleton dynamics may be a promising approach to develop new therapy or biomarker.