Role of mGluR7 in Alzheimer’s disease: pathophysiological insights and therapeutic approaches

Inflammopharmacology. 2025 May 3. doi: 10.1007/s10787-025-01765-3. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterised by oxidative stress, mitochondrial dysfunction, synaptic impairment, and neuronal loss. The progression of AD depends on two main pathologic features, amyloid-beta accumulation, and tau pathology, whereas the disruption of glutamatergic neurotransmission plays an essential role in disease progression. Glutamate, the brain’s primary excitatory neurotransmitter, acts on ionotropic and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptor 7 (mGluR7) is a pre-synaptic type III mGluR receptor playing a crucial role in the central nervous system (CNS) through neurotransmitter modulation, reducing glutamate-induced excitotoxicity, and promoting early neuronal growth. Since mGluR7 is a key regulator of neurotransmitter release, it modulates synaptic integrity and neuronal survival, and its dysfunction is associated with impaired synaptic homeostasis in AD. Moreover, mGluR7 interacts with neuroinflammatory pathways by activating microglia and regulating cytokine production, therefore playing a significant role in AD pathogenesis. The drugs targeting mGluR7, including mGluR7 agonists, antagonists, and allosteric modulators, could potentially be among the most effective agents for the treatment of psychiatric disorders, neurodegenerative diseases including AD, as well as neurodevelopmental impairments, though these potential therapies remain in the early stages. This article summarises the structure as well as the function of mGluR7 and explores current insights into the functioning of mGluR7 in molecular mechanisms of AD pathogenesis. It also discusses potential therapeutic targets of mGluR7, highlighting the need to develop such therapies to prevent disease progression.

PMID:40316832 | DOI:10.1007/s10787-025-01765-3