ENTPDases from Pathogenic Trypanosomatids and Purinergic Signaling: Shedding Light towards Biotechnological Applications

Abstract

: ENTPDases are enzymes known for hydrolyzing extracellular nucleotides and playing an essential role in controlling the nucleotide signaling via nucleotide/purinergic receptors P2. Moreover, ENTPDases, together with Ecto-5´-nucleotidase activity, affect the adenosine signaling via P1 receptors. These signals control many biological processes, including the immune system. In this context, ATP is considered as a trigger to inflammatory signaling, while adenosine (Ado) induces anti-inflammatory response. The trypanosomatids Leishmania and Trypanosoma cruzi, pathogenic agents of Leishmaniasis and Chagas Disease, respectively, have their own ENTPDases named “TpENTPDases,” which can affect the nucleotide signaling, adhesion and infection, in order to favor the parasite. Besides, TpENTPDases are essential for the parasite nutrition, since the Purine De Novo synthesis pathway is absent in them, which makes these pathogens dependent on the intake of purines and nucleopurines for the Salvage Pathway, in which TpENTPDases also take place. Here, we review information regarding TpNTPDases, including their known biological roles and their effect on the purinergic signaling. We also highlight the roles of these enzymes in parasite infection and their biotechnological applications, while pointing to future developments.

E-NTPDases: Possible Roles on Host-Parasite Interactions and Therapeutic Opportunities

“…(2018) seems due to the absence of specificity of Suramin, acting on both P2 receptors and T. cruzi E-NTPDase. These results reinforce the importance of working with specific E-NTPDase inhibitors, whose absence has become an obstacle to be overcome ( da Silva et al., 2021 ).…”

“…Biochemical characterization showed that Tc NTPDase 1 is an Apyrase/CD39/E-NTPDase family member. Moreover, Tc NTPDase1 activity on T. cruzi membrane has also been demonstrated ( Bisaggio et al., 2003 ; Fietto et al., 2004 ; Meyer-Fernandes et al., 2004 ; Santos et al., 2009 ; Giarola et al., 2013 ; Mariotini-Moura et al., 2014 ; da Silva et al., 2021 ).…”

“…Since E-NTPDases have been implicated in different processes of parasite physiology, such as differentiation, nutrition, invasion, survival in the host cell, and modulation of the host immune response to establish infection, these enzymes have been seen as promising targets for drug development ( Paes-Vieira et al., 2018 ). In this sense, many works have shown the effects of several compounds on parasite E-NTPDases ( Knowles, 2011 ; Pimentel et al., 2016 ; de Carvalho et al., 2019 ; da Silva et al., 2021 ).…”

“…In T. cruzi , only one gene coding for Tc NTPDase is present in its genome, named Tc NTPDase 1 ( Fietto et al., 2004 ; da Silva et al., 2021 ). The Tc NTPDase 1 coding sequence has been cloned and expressed in the bacterial system.…”

Targeting P2 receptors in purinergic signaling: a new strategy of active ingredients in traditional Chinese herbals for diseases treatment

“…The hydrolyzed ATP starts working after binding to P2R and then ecto-ATPases on the surface of most cells extract one and two phosphorus atoms of ATP, turning them into ADP and AMP, respectively, or even adenosine alone [8,9]. In addition, ectonuleoside triphosphate phoshohydrolases (ENTPDases), eto-5'-nucleotidase (5'-NT), eto-nucleotide pyrophosphatase/phosphodoesterases (ENPPs), and alkaline phosphatases (APs) are involved in the degradation of ATP [10][11][12]. ATP signaling can be classified into short term and long term [13].…”