A positive allosteric modulator of mGluR5 promotes neuroprotective effects in mice models of Alzheimer's disease.

A positive allosteric modulator of mGluR5 promotes neuroprotective effects in mice models of Alzheimer's disease. Neuropharmacology. 2019 Sep 18;:107785 Authors: Bellozi PMQ, Gomes GF, Machado da Silva MC, Vieira de Assis Lima I, Batista CRÁ, de Oliveira Carneiro Junior W, Dória JG, Vieira ÉLM, Vieira RP, de Freitas RP, Ferreira CN, Candelario-Jalil E, Wyss-Coray T, Ribeiro FM, de Oliveira ACP Abstract Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder. Despite advances in the understanding of its pathophysiology, none of the available therapies prevents disease progression. Excess glutamate plays an important role in excitotoxicity by activating ionotropic receptors. However, the mechanisms modulating neuronal cell survival/death via metabotropic glutamate receptors (mGluRs) are not completely understood. Recent data indicates that CDPPB, a positive allosteric modulator of mGluR5, has neuroprotective effects. Thus, this work aimed to investigate CDPPB treatment effects on amyloid-β (Aβ) induced pathological alterations in vitro and in vivo and in a transgenic mouse model of AD (T41 mice). Aβ induced cell death in primary cultures of hippocampal neurons, which was prevented by CDPPB. Male C57BL/6 mice underwent stereotaxic surgery for unilateral intra-hippocampal Aβ injection, which induced memory deficits, neurodegeneration, neuronal viability reduction and decrease of doublecortin-positive cells, a mar...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research