AUTHOR=Dal Prà Ilaria , Armato Ubaldo , Chiarini Anna TITLE=Family C G-Protein-Coupled Receptors in Alzheimer’s Disease and Therapeutic Implications JOURNAL=Frontiers in Pharmacology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01282 DOI=10.3389/fphar.2019.01282 ISSN=1663-9812 ABSTRACT=
Alzheimer’s disease (AD), particularly its sporadic or late-onset form (SAD/LOAD), is the most prevalent (96–98% of cases) neurodegenerative dementia in aged people. AD’s neuropathology hallmarks are intrabrain accumulation of amyloid-β peptides (Aβs) and of hyperphosphorylated Tau (p-Tau) proteins, diffuse neuroinflammation, and progressive death of neurons and oligodendrocytes. Mounting evidences suggest that family C G-protein-coupled receptors (GPCRs), which include γ-aminobutyric acid B receptors (GABABRs), metabotropic glutamate receptors (mGluR1-8), and the calcium-sensing receptor (CaSR), are involved in many neurotransmitter systems that dysfunction in AD. This review updates the available knowledge about the roles of GPCRs, particularly but not exclusively those expressed by brain astrocytes, in SAD/LOAD onset and progression, taking stock of their respective mechanisms of action and of their potential as anti-AD therapeutic targets. In particular, GABABRs prevent Aβs synthesis and neuronal hyperexcitability and group I mGluRs play important pathogenetic roles in transgenic AD-model animals. Moreover, the specific binding of Aβs to the CaSRs of human cortical astrocytes and neurons cultured