RGD Reference Report - The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity. - Rat Genome Database

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The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity.

Authors: Wang, X  Sirianni, A  Pei, Z  Cormier, K  Smith, K  Jiang, J  Zhou, S  Wang, H  Zhao, R  Yano, H  Kim, JE  Li, W  Kristal, BS  Ferrante, RJ  Friedlander, RM 
Citation: Wang X, etal., J Neurosci. 2011 Oct 12;31(41):14496-507. doi: 10.1523/JNEUROSCI.3059-11.2011.
RGD ID: 9686058
Pubmed: PMID:21994366   (View Abstract at PubMed)
PMCID: PMC3213696   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3059-11.2011   (Journal Full-text)

Melatonin mediates neuroprotection in several experimental models of neurodegeneration. It is not yet known, however, whether melatonin provides neuroprotection in genetic models of Huntington's disease (HD). We report that melatonin delays disease onset and mortality in a transgenic mouse model of HD. Moreover, mutant huntingtin (htt)-mediated toxicity in cells, mice, and humans is associated with loss of the type 1 melatonin receptor (MT1). We observe high levels of MT1 receptor in mitochondria from the brains of wild-type mice but much less in brains from HD mice. Moreover, we demonstrate that melatonin inhibits mutant htt-induced caspase activation and preserves MT1 receptor expression. This observation is critical, because melatonin-mediated protection is dependent on the presence and activation of the MT1 receptor. In summary, we delineate a pathologic process whereby mutant htt-induced loss of the mitochondrial MT1 receptor enhances neuronal vulnerability and potentially accelerates the neurodegenerative process.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Huntington's disease treatmentISOMtnr1a (Mus musculus)9686058; 9686058 RGD 
Huntington's disease  IEP 9686058mRNA:decreased expression:brainRGD 
Huntington's disease  ISOMTNR1A (Homo sapiens)9686058; 9686058mRNA:decreased expression:brainRGD 
Huntington's disease treatmentIEP 9686058 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtnr1a  (melatonin receptor 1A)

Genes (Mus musculus)
Mtnr1a  (melatonin receptor 1A)

Genes (Homo sapiens)
MTNR1A  (melatonin receptor 1A)


Additional Information