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

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

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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