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Neuroendocrine and neurotrophic signaling in Huntington's disease:Implications for pathogenic mechanisms and treatment strategies
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
Hypothalamo-Hypophyseal System
Cognitive Neuroscience
Hypothalamus
Pituitary-Adrenal System
Disease
Melatonin
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Huntington's disease
Neurotrophic factors
medicine
Huntingtin Protein
Humans
Circadian rhythm
Hypothalamic-pituitary-adrenal (HPA) axis
biology
Brain-Derived Neurotrophic Factor
Polyglutamine tract
medicine.disease
3. Good health
Huntington Disease
030104 developmental biology
Neuropsychology and Physiological Psychology
Suprachiasmatic nucleus (SCN)
biology.protein
Brain-derived neurotrophic factor (BDNF)
Sleep
Psychology
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Neurotrophin
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9f2dc4e7c5a4187a68e6e61eebda26d3