Nov 14, 2019

Family C G-Protein-Coupled Receptors in Alzheimer's Disease and Therapeutic Implications

Frontiers in Pharmacology
Ilaria Dal PràAnna Chiarini

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 in vitro engenders a pathol...Continue Reading

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Mentioned in this Paper

In Vivo
Peptide Biosynthesis
G-Protein-Coupled Receptors
Vascular Endothelial Cells
Neurons
Brain
Receptors, Metabotropic Glutamate
Cessation of Life
EED
Molecular_function

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