DAPK1 Promotes Extrasynaptic GluN2B Phosphorylation and Striatal Spine Instability in the YAC128 Mouse Model of Huntington Disease.

ABSTRACT: Huntington disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Disrupted cortico-striatal transmission is an early event that contributes to neuronal spine and synapse dysfunction primarily in striatal medium spiny neurons, the most vulnerable cell type in the disease, but also in neurons of other brain regions including the cortex. Although striatal and cortical neurons eventually degenerate, these synaptic and circuit changes may underlie some of the earliest motor, cognitive, and psychiatric symptoms. Moreover, synaptic dysfunction and spine loss are hypothesized to be therapeutically reversible before neuronal death occurs, and restoration of normal synaptic function may delay neurodegeneration. One of the earliest synaptic

SUBMITTER: Schmidt ME 

PROVIDER: S-EPMC7674490 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature