@article{APS9486,
author = {Ohad STOLER and Ilya A FLEIDERVISH},
title = {Functional implications of axon initial segment cytoskeletal disruption in stroke},
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {1},
year = {2017},
keywords = {},
abstract = {Axon initial segment (AIS) is the proximal part of the axon, which is not covered with a myelin sheath and possesses a distinctive, specialized assembly of voltage-gated ion channels and associated proteins. AIS plays critical roles in synaptic integration and action potential generation in central neurons. Recent evidence shows that stroke causes rapid, irreversible calpain-mediated proteolysis of the AIS cytoskeleton of neurons surrounding the ischemic necrotic core. A better understanding of the molecular mechanisms underlying this “non-lethal” neuronal damage might provide new therapeutic strategies for improving stroke outcome. Here, we present a brief overview of the structure and function of the AIS. We then discuss possible mechanisms underlying stroke-induced AIS damage, including the roles of calpains and possible sources of Ca2+ ions, which are necessary for the activation of calpains. Finally, we discuss the potential functional implications of the loss of the AIS cytoskeleton and ion channel clusters for neuronal excitability.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9486}
}