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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Neurotrophin Receptor Signaling as a Therapeutic Target for Huntington's Disease

Author(s): Danielle A. Simmons, Frank M. Longo and Stephen M. Massa*

Volume 16, Issue 3, 2017

Page: [291 - 302] Pages: 12

DOI: 10.2174/1871527315666161107093047

Price: $65

Abstract

Effective non-genetic disease modifying treatments for Huntington’s disease (HD) will necessarily target multiple diverse neurodegenerative processes triggered by mutant huntingtin. Neurotrophin receptors are well-positioned for this task as they regulate signaling pathways that largely overlap with signaling networks contributing to HD-related synaptic dysfunction, glial activation, excitotoxicity, and other degenerative processes. This review will discuss the contributions of disrupted neurotrophin receptor-related signaling to primary HD neuropathologies, and prospects for harnessing this signaling to develop therapeutics to counteract HD degenerative mechanisms. Application of the native protein ligands has been challenging pharmacologically, but progress has been made with the advent of small molecule compounds that can selectively bind to and activate specific Trk receptors or p75NTR to promote trophic and/or inhibit degenerative signaling in cell populations preferentially affected in HD.

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