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Updated: May 28, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity
Xin Wang1, Ana Sirianni, Zhijuan Pei
1Neuroapoptosis Laboratory and Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. xwang@rics.bwh.harvard.edu
Summary
Melatonin delays Huntington
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neurodegenerative diseases like Huntington's disease (HD) pose significant challenges.
- Melatonin is known to offer neuroprotection in various experimental models.
- The role of melatonin in genetic models of Huntington's disease remains unexplored.
Purpose of the Study:
- To investigate the neuroprotective effects of melatonin in a genetic model of Huntington's disease.
- To explore the association between mutant huntingtin toxicity and the type 1 melatonin receptor (MT1).
Main Methods:
- Utilized a transgenic mouse model of Huntington's disease.
- Assessed disease onset, mortality, and MT1 receptor expression in brain mitochondria.
- Investigated the impact of melatonin on mutant huntingtin-induced toxicity and caspase activation in cellular and animal models.
Main Results:
- Melatonin administration delayed disease onset and reduced mortality in HD mice.
- Mutant huntingtin toxicity correlated with a significant loss of the MT1 receptor, particularly in brain mitochondria.
- Melatonin treatment inhibited mutant huntingtin-induced caspase activation and preserved MT1 receptor expression.
Conclusions:
- Melatonin demonstrates neuroprotective effects in a genetic model of Huntington's disease.
- The neuroprotection offered by melatonin is dependent on the presence and activation of the MT1 receptor.
- Loss of mitochondrial MT1 receptor due to mutant huntingtin contributes to neuronal vulnerability and disease progression in HD.
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