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.
RAS ID
22110
Document Type
Journal Article
Date of Publication
2016
Location of the Work
United Kingdom
Funding Information
Lotterywest (#G0002718)
NHMRC Senior Research Fellowships (#513704 and #1004475)
Jacques and Gloria Gossweiler Foundation, Bern, Switzerland
School
School of Medical and Health Sciences
Grant Number
NHMRC Number : 513704, 1004475
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Publisher
Pergamon Press
Recommended Citation
Bartlett, D., Cruickshank, T. M., Hannan, A. J., Eastwood, P. R., Lázár, A. S., & Ziman, M. R. (2016). Neuroendocrine and neurotrophic signaling in Huntington's disease: Implications for pathogenic mechanisms and treatment strategies. DOI: https://doi.org/10.1016/j.neubiorev.2016.09.006
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