Distinct Roles of AMPA Receptor Subunits as Potential Therapeutic Targets in Alzheimer's Disease.

Abstract

AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and play central roles in synaptic plasticity, learning, and memory. They are heterotetrameric complexes organized as two dimers, with subunits from GluA1 to GluA4. Dysregulation of AMPAR trafficking, localization, and function has been increasingly implicated in amyloid beta (Aβ)- and tau-associated synaptic deficits, which are the pathological hallmarks for Alzheimer's disease (AD). Accumulating evidence suggests that AMPARs play distinct, subunit-specific roles in synaptic plasticity and learning and memory in physiological and pathological contexts. This review synthesizes current understanding of subunit-specific AMPAR-mediated pathological mechanisms in AD and discusses emerging pharmacological strategies targeting AMPARs as potential therapeutic approaches to delay or attenuate disease progression.