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axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders

Neural Regeneration Research 2021年第10期16卷 1901-1910页

作者： Katherine L.Marshall Mohamed H.Farah Department of Neurology at Johns Hopkins School of Medicine BaltimoreMDUSA

Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ***-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets,which in turn leads to functional *** the course of many of neurologic diseases,axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse *** amyotrophic lateral sclerosis(ALS),distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron *** is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in ALS that is usually quickly overtaken by the disease *** drugs that enhance compensatory sprouting and encourage reinnervation may slow symptom progression and retain muscle function for a longer period of time in ALS and in other diseases that exhibit dying-back *** remain many outstanding questions as to the impact of distinct disease-causing mutations on axonal outgrowth and regeneration,especially in regards to motor neurons derived from patient induced pluripotent stem *** microfluidic chambers are powerful tools for studying the distal axons of human induced pluripotent stem cells-derived motor neurons,and have recently been used to demonstrate striking regeneration defects in human motor neurons harboring ALS disease-causing *** the human neuromuscular circuit with human induced pluripotent stem cells-derived motor neurons will be critical for developing drugs that enhance axonal regeneration,sprouting,and reinnervation of neuromuscular *** this review we will discuss compensatory axonal sprouting as a potential therapeutic target for ALS,and the use of compartmentalized microfluidic devices to find drugs that enhance regeneration and axonal sprouting of motor axons.

关键词： amyotrophic lateral sclerosis axonal regeneration dying-back axonopathy in vitro neuromuscular junction iPSC-derived motor neurons microfluidic device motor axon sprouting

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