Zinc-mediated neurotransmission in Alzheimer's disease: A potential role of the GPR39 in dementia.

Zinc-mediated neurotransmission in Alzheimer's disease: A potential role of the GPR39 in dementia. Curr Neuropharmacol. 2019 Jul 04;: Authors: Rychlik M, Mlyniec K Abstract With more people reaching an advanced age in modern society, there is a growing need for strategies to slow down age-related neuropathology and loss of cognitive functions, which are a hallmark of Alzheimer's disease. Neuroprotective drugs and candidate drug compounds target one or more processes involved in the neurodegenerative cascade, such as excitotoxicity, oxidative stress, misfolded protein aggregation and/or ion dyshomeostasis. A growing body of research shows that a G-protein coupled zinc (Zn2+) receptor (GPR39) can modulate the abovementioned processes. Zn2+ itself has a diverse activity profile at the synapse, and by binding to numerous receptors, it plays an important role in neurotransmission. However, Zn2+ is also necessary for the formation of toxic oligomeric forms of amyloid beta, which underlie the pathology of Alzheimer's disease. Furthermore, the binding of Zn2+ by amyloid beta causes a disruption of zincergic signaling, and recent studies point to GPR39 and its intracellular targets being affected by amyloid pathology. In this review we present neurobiological findings related to Zn2+ and GPR39, focusing on its signaling pathways, neural plasticity, interactions with other neurotransmission systems, as well as on the effects of pathophysiologi...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research