The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases

Abstract

Evidences show that purinergic signaling is involved in processes associated with health and disease, including noncommunicable, neurological, and degenerative diseases. These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. These pathological conditions can be associated with disturbance in the signaling mediated by nucleotides and nucleosides of adenine, in expression or activity of extracellular ectonucleotidases and in activation of P2X and P2Y receptors. Among the best known of these diseases are atherosclerosis, hypertension, cancer, epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The currently available treatments present limited effectiveness and are mostly palliative. This review aims to present the role of purinergic signaling highlighting the ectonucleotidases E-NTPDase, E-NPP, E-5′-nucleotidase, and adenosine deaminase in noncommunicable, neurological, and degenerative diseases associated with the cardiovascular and central nervous systems and cancer. In conclusion, changes in the activity of ectonucleotidases were verified in all reviewed diseases. Although the role of ectonucleotidases still remains to be further investigated, evidences reviewed here can contribute to a better understanding of the molecular mechanisms of highly complex diseases, which majorly impact on patients' quality of life.

Acute moderate‐intensity aerobic exercise promotes purinergic and inflammatory responses in sedentary, overweight and physically active subjects

“…Our results may reflect the nucleotidase behaviour at different time points post-exercise, taking into account that moderate and intense acute exercise promote transitory pro-inflammatory and pro-thrombotic responses, such as increasing the plasma levels of lymphocytes, natural killer (NK) cells, IL-6, IL-8, C-reactive protein, platelet count, β-thromboglobulin, thrombin/antithrombin complexes and sensitivity to collagen-and ADP-induced aggregation (Cerqueira et al, 2020;Lippi & Maffulli, 2009;Posthuma et al, 2015). With regard to the immuno-and thromboregulatory roles of NTPDases, NPPs and 5′-NT, it is plausible that a purinergic signalling pathway may be triggered in an attempt to control the pro-thrombotic and pro-inflammatory effects of acute exercise through modulation of nucleotide and nucleoside levels (Bagatini et al, 2018;Yegutkin, 2021).…”

Epigenome-wide association study of level and change in cognitive abilities from midlife through late-life

“…ENTPD8 is a member of the E-NTPDase family, enzymes involved ATP metabolism, and, according to the Human Protein Atlas (22), expressed mainly in the intestine. While still poorly understood, there is evidence of purinergic signaling involved in neurological and degenerative disease, including AD, Parkinson's disease, and multiple sclerosis (30).…”

Modulatory effect of ursolic acid on neurodegenerative activities in oxidative brain injury: Anex vivostudy

“…Altered purinergic enzyme activities has been linked to disturbances in energetic metabolism as they hydrolyze adenosine triphosphate (ATP) and adenosine monophosphate (AMP) to yield the endogenous signaling nucleotide, adenosine (Akinyemi et al, 2017;Bagatini et al, 2018). These alterations depict a pu- Depleted ATP levels can be correlated with perturbance in cellular energy metabolism.…”