Update on huntington’s disease

Abstract

Huntington's disease (HD) is a devastating neurodegenerative disease causing progressive movement disorders, cognitive dysfunction, and behavioral changes. Since the causative mutation of an expanded polyglutamine repeat in the huntingtin gene was identified, significant progress has been achieved in elucidating pathogenic mechanisms. This review summarizes recent developments in evaluating the role of abnormal protein aggregation, transcriptional dysregulation, mitochondrial and bioenergetic dysfunction, excitotoxicity, and abnormal cellular trafficking in the pathogenesis of HD. In addition, although therapeutic options in HD have been limited, progress in developing targeted therapies continues, and these advancements and future directions are reviewed.

Dextromethorphan as a Potential Neuroprotective Agent With Unique Mechanisms of Action

“…19,118,119 Although the results of 3 small DM clinical studies in ALS were negative, 68 -70 1 of these nevertheless showed a reduced decline in lower extremity function with DM. 68 Furthermore, these studies used subneuroprotective doses.…”

N-Terminal Proteolysis of Full-Length Mutant Huntingtin in an Inducible PC12 Cell Model of Huntington’s Disease

“…[3][4][5][6][7][8] Cellular toxicity in HD may involve interference of expanded Htt with gene transcription, vesicle transport, mitochondrial function, Ca 2+ homeostasis, and protein degradation machinery via proteasome or autophagy. [9][10][11][12][13][14][15] The nature of cytotoxic species of expanded Htt is unknown, but there is emerging evidence suggesting that they might be generated via Htt proteolysis. The main pathological feature of all CAG repeat disorders is the formation of nuclear and cytoplasmic inclusions in neurons of affected brain regions.…”