Strain hypothesis and additional evidence of the GluN3A deficiency-mediated pathogenesis of Alzheimer's disease.

ABSTRACT: Our recent investigation revealed that deficiency of N-methyl-D-aspartate (NMDA) receptor subunit GluN3A (NR3A) is a trigger for chronic neuronal hyperactivity and disruptionFfepspof Ca²⁺ homeostasis, leading to sporadic Alzheimer's disease (AD) phenotypes. The identification of the amyloid-independent pathogenesis was a surprise considering that GluN3A is a much less known NMDA receptor subunit with obscure function in aging adulthood, while the new concept of degenerative excitotoxicity as a decade-long pathogenic mechanism of AD/dementia remains to be further delineated. With negative observations in GRIN3A-/- mouse, Verhaeghe et al. in their letter challenge the "odd" idea that lasting GluN3A deficiency is detrimental and responsible for the spontaneous progression of AD and

SUBMITTER: Yu SP 

PROVIDER: S-EPMC10528065 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature