Adenosine Type A2A Receptor in Peripheral Cell from Patients with Alzheimer’s Disease, Vascular Dementia, and Idiopathic Normal Pressure Hydrocephalus: A New/Old Potential Target

Abstract

U n c o r r e c t e d A u t h o r P r o o fJournal of Alzheimer's Disease xx (20xx) Abstract. As the European population gets older, the incidence of neurological disorders increases with significant impact on social costs. Despite differences in disease etiology, several brain disorders in the elderly (e.g., Alzheimer's disease, vascular dementia, normal pressure hydrocephalus) share dementia as a common clinical feature. The current treatment for the majority of these diseases is merely symptomatic and does not modify the course of the illness. Symptoms of normal pressure hydrocephalus are the only ones that can be modified if they are recognized in time and treated appropriately. Therefore, an important clinical strategy may be disclosed by pathogenic pathways that can be modified and to find drugs that can slow down or even arrest disease progression. Possibly a way to answer this question could be by re-examining all the molecules which have so far succeeded in improving many aspects of cognitive deterioration in some neurodegenerative conditions, that were not considered because of controversial opinions. The main purpose of this summary is to further substantiate the hypothesis that the pathway of adenosine type A 2A receptor could be used as a potential target to develop new/old therapeutic strategies.

Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats

“…The roles of exogenous and endogenous purine nucleosides in the central nervous system are currently under intense investigation (Ipata, 2011; Ribeiro et al, 2016; Fumagalli et al, 2017). Adenosine is an endogenous neuromodulator implicated in the pathophysiology of various neurological diseases including epilepsy, stroke, chronic pain, and dementia (Sollevi, 1997; Boison, 2005; Arosio et al, 2016). The physiological functions of this nucleoside in the nervous system are exerted by binding to G-protein coupled receptors, which are classified into four categories: A1, A2A, A2B, and A3 (Zhou et al, 1992).…”

Targeting Adenosine Receptors in Neurological Diseases

“…A2A receptor activation in AD can prevent the cognitive impairment and memory loss. In a study of mice models, an oral dose of a selective antagonist of A2A receptor decreased tau hyperphosphorylation and improved spatial memory in AD (Arosio et al, 2016).…”

Adenosine A2A Receptors as Biomarkers of Brain Diseases

“…A 2A R are not only located in the brain, but are also present in several peripheral tissues, namely in different blood cells such as leukocytes and platelets (reviewed in Gessi et al, 2000). Based on the association of brain diseases with A 2A R up-regulation in afflicted brain regions, several studies explored if A 2A R in blood cells could be biomarkers of brain diseases, such as AD (Arosio et al, 2010(Arosio et al, , 2016Merighi et al, 2021), PD (Falconi et al, 2019), or ALS (Vincenzi et al, 2013). However, only the understanding of the mechanisms underlying A 2A R up-regulation in brain diseases will allow providing a rationale (or lack of thereof) to consider alterations of the density of peripheral A 2A R as valid readouts of altered A 2A R density that occurs selectively in afflicted brain circuits in the diseased brain.…”