Metabotropic glutamate receptor (mGlu3R) splicing variants in aging and Alzheimer´s disease

Abstract

Subtype 3 metabotropic glutamate receptors (mGlu3R) promote several neuroprotective effects, especially in glial cells. We have previously demonstrated that mGlu3R activation in astrocytes promotes the non-amyloidogenic cleavage of amyloid precursor protein and induces the release of neurotrophin sAPPα, whereas it also increases Aβ uptake by astrocytes, which consequently improves neuron survival in co-culture systems. It is known that a truncated version of the receptor, called mGlu3Δ4R, which lacks the transmembrane domain and has been linked to a schizophrenic status, acts as a negative modulator of mGlu3R. In fact, mGlu3Δ4R is able to interact with canonical mGlu3R thereby inhibiting the functional mGlu3R homodimerization. ...