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REVIEW
Year : 2021  |  Volume : 16  |  Issue : 10  |  Page : 1901-1910

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


Department of Neurology at Johns Hopkins School of Medicine, Baltimore, MD, USA

Correspondence Address:
Mohamed H Farah
Department of Neurology at Johns Hopkins School of Medicine, Baltimore, MD
USA
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Source of Support: This work was supported by the Muscular Dystrophy Association, No. W81XWH1910229 (to MHF) from Department of Defense’s Congressionally Directed Medical Research Program, and Maryland Stem Cell Research Fund, No. 2019-MSCRFD-5093 (to MHF), Conflict of Interest: None


DOI: 10.4103/1673-5374.308077

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Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ages. Dying-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets, which in turn leads to functional impairment. During the course of many of neurologic diseases, axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse function. In amyotrophic lateral sclerosis (ALS), distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron death. There is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in ALS that is usually quickly overtaken by the disease course. Potential 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 axonopathy. There 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 cells. Compartmentalized 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 mutations. Modeling 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 junctions. In 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.


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