The role of opioid receptors in modulating Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a complex neurological disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Long term investigation of AD pathogenesis suggests that β-site amyloid precursor protein [APP] cleaving enzyme 1 (BACE1) and γ-secretase enzymes promote the amyloidogenic pathway and produce toxic Aβ peptides that are predisposed to aggregate in the brain. Hence, the targeted inhibition of BACE1/γ-secretase expression and function is a promising approach for AD therapy. Several reports have suggested that the opioid family of G-protein coupled receptors modulate the etiology of AD progression. It has also been found that changes in the signaling pathways of opioid receptors increased the expression of BACE1 and γ-secretase, and is strongly correlated with abnormal production of Aβ and pathogenesis of AD. Thus, the opioid receptor family is a promising candidate for targeted drug development to treat AD. In this review, we outline the involvement and mechanisms of opioid receptor signaling modulation in Alzheimer’s Disease progression.

Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors

“…Since DORs are involved in controlling the dorsal hippocampal-striatal balance, DOR knockout mice presented impairment of dorsal hippocampus-dependent tasks, including associative learning, when the balance was biased towards facilitated striatal function [289]. Alteration of opioid receptor signaling increased gene expression implicated in Aβ production, thereby contributing to Alzheimer's disease (AD) pathogenesis [290]. In conclusion, the results mentioned above make GABAergic and opioidergic signaling pathways a promising clinical perspective for the therapeutic purpose of neurodevelopment/neurodegenerative diseases.…”