mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington’s disease

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Science Signaling  19 Dec 2017:
Vol. 10, Issue 510, eaan6387
DOI: 10.1126/scisignal.aan6387

A treatment for Huntington’s disease?

There are currently no therapies that stop or reverse Huntington’s disease (HD), a progressive neurodegenerative disease caused by an expansion in the huntingtin protein that promotes its toxic accumulation in the central nervous system. Impaired autophagy, the process of breaking down and removing cellular debris and dysfunctional proteins, is implicated in HD. Blocking the kinase mTOR therapeutically can activate autophagy, but these drugs have serious side effects and poor penetrance into the brain. Abd-Elrahman et al. found that inhibiting the neuronal cell-surface glutamate receptor mGluR5 with the drug CTEP stimulated autophagy of huntingtin aggregates and improved motor and cognitive performance in HD model mice, without any apparent side effects. Given that CTEP analog is already in clinical trials for other neuronal-associated disorders, these findings suggest that the trials ought to be expanded to include HD patients.

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