Chapter 28 - Neurotransmitter receptors in Alzheimer's disease: from glutamatergic to cholinergic receptors

Abstract

The receptors for neurotransmitters are modulated by the signaling pathways of the brain in response to physiological adaptations, pharmacological treatments, or pathological status to maintain the homeostasis of the nervous circuitry. The clinical manifestations of Alzheimer's disease (AD) are a consequence of the impairment in these cerebral pathways, among which the basal forebrain cholinergic innervation of cortical areas is the most vulnerable. Consequently, the cholinergic receptors are regulated during the progression of AD, but the regulation of receptors for other endogenous neurotransmitters has also been described in patients and in different experimental and animal models. The main receptors implicated in AD symptoms are the AMPA and NMDA glutamatergic receptors, ionotropic and metabotropic receptors for GABA, β2 noradrenergic receptors, D2 dopaminergic receptors, serotonergic 5-HT6 receptors, and the cholinergic nicotinic α7, and muscarinic M1 or M2 subtypes. The identification of specific receptor targets in AD has facilitated the research and development of new selective drugs that are reaching clinical trials.