Therapeutic targeting of the pathological triad of extrasynaptic NMDA receptor signaling in neurodegenerations.

ABSTRACT: Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation-transcription coupling caused by CREB (cyclic adenosine monophosphate-responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss. Both acute and slowly progressive neurodegenerative conditions, including stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease, share increased de

SUBMITTER: Bading H 

PROVIDER: S-EPMC5339681 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature