Neuroendocrine and neurotrophic signaling in Huntington's disease:Implications for pathogenic mechanisms and treatment strategies

Bartlett, Danielle M, Cruickshank, Travis M, Hannan, Anthony J, Eastwood, Peter R, Lazar, Alpar S and Ziman, Mel R (2016) Neuroendocrine and neurotrophic signaling in Huntington's disease:Implications for pathogenic mechanisms and treatment strategies. Neuroscience and Biobehavioral Reviews, 71. pp. 444-454. ISSN 0149-7634

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Abstract

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways.

Item Type:	Article
Additional Information:	Published under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence.
Faculty \ School:	Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Dementia & Complexity in Later Life Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User:	Pure Connector
Date Deposited:	07 Dec 2016 00:06
Last Modified:	19 Oct 2023 01:52
URI:	https://ueaeprints.uea.ac.uk/id/eprint/61603
DOI:	10.1016/j.neubiorev.2016.09.006

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