Abstract
Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals. Here, GPCRs’ role in the pathophysiology of different neurodegenerative disease progressions and cognitive deficits has been highlighted, and an emphasis has been placed on the current pharmacological developments with GPCRs to provide an insight into a potential therapeutic target in the treatment of neurodegeneration.
Highlights
G-protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in humans, and ~34% of marketed drugs target this family
Another neuropeptide, are important in social cognition, trust, behaviour, and facial expressions. These neuropeptides are related to the pituitary and synthesised in the hypothalamus, primarily in large magnocellular neurons located in the supraoptic and paraventricular nuclei [41]. They are released into various brain regions, such as the amygdala and anterior cingulate cortex, for the paracrine signalling of the oxytocin receptor (OXTR) and vasopressin receptor (AVPR1a), and these receptors have a pathophysiological impact on Frontotemporal dementia (FTD) [42]
Metabotropic glutamate receptors are members of the C GPCR family, and they consist of eight subtypes that are further subdivided into three groups depending on their amino acid sequences, G-protein coupling, and pharmacological characteristics
Summary
G-protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in humans, and ~34% of marketed drugs target this family Since their discovery, this receptor family has been both pharmacologically and biologically important in the treatment of different pathological conditions. Neurodegenerative diseases (NDDs) are most common and prevalent in elderly people worldwide [2] and cause progressive neuronal dysfunction, toxicities, and death. These diseases lead to an irreversible weakening of all brain functions. Among the various NDDs, AD, which causes impaired cognitive function and memory loss, is the most extensively discussed and researched [8]. The aim is to provide a potential and novel target for the development of novel therapeutics for NDD treatment
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