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Huntington's disease: easing the NMDAR traffic jam

Nature Medicine volume 19, pages 971–973 (2013)Cite this article

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Excitatory neurotransmission through NMDA receptors (NMDARs) has a pivotal role in healthy brain function, and its dysfunction has long been implicated in the pathogenesis of neurodegenerative disorders, including Huntington's disease. A new study uncovers a molecular link between mutant huntingtin and aberrant trafficking of an unconventional NDMAR subunit (GluN3A). Targeting this disease mechanism in a Huntington's disease mouse model had multiple therapeutic benefits (pages 1030–1038).

The proper functioning of the human brain requires effective communication among an estimated 85 billion neurons through 100 trillion synapses. Neurodegenerative disorders, such as Alzheimer's and Huntington's diseases, have gradual but relentless loss of both synapses and neurons, which underlies the impaired motor control, emotional responses, memory and cognition observed in these disorders. A long-standing theory suggests that early synaptic deficits may be a key pathological event in neurodegenerative disease that accounts for the clinical symptoms and eventual neuronal demise1. If so, correcting synaptic dysfunction could be a useful therapeutic strategy for these devastating brain disorders.

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Figure 1: Aberrant mHtt interaction with PACSIN1 impairs endocytosis of the NMDAR subunit GluN3A at synapses in Huntington's disease.

Marina Corral Spence

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Authors and Affiliations

  1. Department of Psychiatry & Biobehavioral Sciences, Anthony Daggett and X. William Yang are at the Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, California, USA.,

    Anthony Daggett & X William Yang

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  1. Anthony Daggett
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  2. X William Yang
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Correspondence to X William Yang.

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Daggett, A., Yang, X. Huntington's disease: easing the NMDAR traffic jam. Nat Med 19, 971–973 (2013). https://doi.org/10.1038/nm.3283

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