Amyloid-beta neurotoxicity and clearance are both regulated by glial group II metabotropic glutamate receptors

Neuropharmacology
Daniela DurandMercedes Lasaga

Abstract

Astrocytes are now fully endorsed as key players in CNS functionality and plasticity. We recently showed that metabotropic glutamate receptor 3 (mGlu3R) activation by LY379268 promotes non-amyloidogenic cleavage of amyloid precursor protein (APP) in cultured astrocytes, leading to increased release of neuroprotective sAPPα. Furthermore, mGlu3R expression is reduced in hippocampal astrocytes from PDAPP-J20 mice, suggesting a role for these receptors in Alzheimer's disease. The present study enquires into the role of astroglial-derived neurotrophins induced by mGlu3R activation in neurotoxicity triggered by amyloid β (Aβ). Conditioned medium from LY379268-treated astrocytes protected hippocampal neurons from Aβ-induced cell death. Immunodepletion of sAPPα from the conditioned medium prevented its protective effect. LY379268 induced brain-derived neurotrophic factor (BDNF) expression in astrocytes, and neutralizing BDNF from conditioned medium also prevented its neuroprotective effect on Aβ neurotoxicity. LY379268 was also able to decrease Aβ-induced neuron death by acting directly on neuronal mGlu3R. On the other hand, LY379268 increased Aβ uptake in astrocytes and microglia. Indeed, and more importantly, a reduction in Aβ-induce...Continue Reading

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Citations

Sep 7, 2018·Frontiers in Cellular Neuroscience·Md Ezazul HaqueDong-Kug Choi
Nov 14, 2019·Frontiers in Pharmacology·Ilaria Dal PràAnna Chiarini
Nov 30, 2018·Frontiers in Molecular Neuroscience·Simona Federica SpampinatoFilippo Caraci
Dec 15, 2020·Journal of Neurochemistry·Nofar Stolero, Dan Frenkel
Jan 8, 2021·Journal of Neuroinflammation·Manuela ZinniOlivier Baud
Oct 15, 2020·International Journal of Molecular Sciences·Vidyasagar Naik BukkeTommaso Cassano
Aug 29, 2020·Neurochemistry International·Juan TuratiMercedes Lasaga
Aug 26, 2021·Neuropharmacology·Ulyana LaloYuriy Pankratov

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