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.
Highlights
Noncommunicable, neurological, and degenerative diseases are characterized by cell loss, leading to deterioration in quality or function of tissues or organs and possible failure of vital organs [1]
The control of the levels of extracellular nucleotides adenine and adenosine and the consequent signaling by purinergic receptors induced by them is critical in maintaining the physiological processes [5]
This review summarizes the most current knowledge on the role of families of nucleotide metabolizing enzymes, the ectonucleotidases, on degenerative diseases
Summary
Noncommunicable, neurological, and degenerative diseases are characterized by cell loss, leading to deterioration in quality or function of tissues or organs and possible failure of vital organs [1]. Elucidation of common and unique mechanisms responsible for the deterioration present in these pathologies may facilitate the identification and development of effective targets and therapies [2]. The control of the levels of extracellular nucleotides adenine and adenosine and the consequent signaling by purinergic receptors induced by them is critical in maintaining the physiological processes [5]. This control is performed by ectonucleotidases, which are enzymes anchored to the cell surface or located in the interstitial medium (soluble form) [6]
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