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

Authors

Danielle Bartlett, Edith Cowan UniversityFollow
Travis M. Cruickshank, Edith Cowan UniversityFollow
Anthony J. Hannan, University of Melbourne
Peter R. Eastwood, Sir Charles Gairdner Hospital
Alpár S. Lázár, University of Cambridge
Mel R. Ziman Dr, Edith Cowan UniversityFollow

Document Type

Journal Article

Publisher

Pergamon Press

Place of Publication

United Kingdom

School

School of Medical and Health Sciences

RAS ID

22110

Funders

Lotterywest (#G0002718)

NHMRC Senior Research Fellowships (#513704 and #1004475)

Jacques and Gloria Gossweiler Foundation, Bern, Switzerland

Grant Number

NHMRC Number : 513704, 1004475

Grant Link

http://purl.org/au-research/grants/nhmrc/513704

http://purl.org/au-research/grants/nhmrc/1004475

Comments

Bartlett, D. M., Cruickshank, T. M., Hannan, A. J., Eastwood, P. R., Lazar, A. S., & Ziman, M. R. (2016). Neuroendocrine and neurotrophic signaling in Huntington’s disease: implications for pathogenic mechanisms and treatment strategies. Neuroscience & Biobehavioral Reviews, 71, 444-454.

https://doi.org/10.1016/j.neubiorev.2016.09.006

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.

DOI

10.1016/j.neubiorev.2016.09.006

Related Publications

Bartlett, D. M. (2018). The utility of multidisciplinary rehabilitation as a treatment strategy for circadian rhythm and sleep disturbances in premanifest Huntington’s Disease. Retrieved from https://ro.ecu.edu.au/theses/2143

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