P2X Receptors: Potential Therapeutic Targets for Symptoms Associated With Lung Cancer - A Mini Review.
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ABSTRACT:
SUBMITTER: Mai Y
PROVIDER: S-EPMC8276243 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sigma receptors comprise a unique family of proteins that have been implicated in the pathophysiology and treatment of many central nervous system disorders, consistent with their high level of expression in the brain and spinal cord. Mounting evidence indicate that targeting sigma receptors may be particularly beneficial in a number of neurodegenerative conditions including Alzheimer׳s disease, Parkinson׳s disease, stroke, methamphetamine neurotoxicity, Huntington׳s disease, amyotrophic lateral sclerosis, and retinal degeneration. In this perspective, a brief overview is given on sigma receptors, followed by a focus on common mechanisms of neurodegeneration that appear amenable to modulation by sigma receptor ligands to convey neuroprotective effects and/or restorative functions. Within each of the major mechanisms discussed herein, the neuroprotective effects of sigma ligands are summarized, and when known, the specific sigma receptor subtype(s) involved are identified. Together, the literature suggests sigma receptors may provide a novel target for combatting neurodegenerative diseases through both neuronal and glial mechanisms.
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Project description:Purinergic receptors play important roles in central nervous system (CNS), where the bulk of these receptors are implicated in neuroinflammatory responses and regulation of cellular function of neurons, microglial and astrocytes. Within the P2X receptor family, P2X7 receptor is generally known for its inactivity in normal conditions and activation by moderately high concentrations (>100 μM) of extracellular adenosine 5'-triphosphate (ATP) released from injured cells as a result of brain injury or pathological conditions. Activation of P2X7R contributes to the activation and proliferation of microglia and directly contribute to neurodegeneration by provoking microglia-mediated neuronal death, glutamate-mediated excitotoxicity, and NLRP3 inflammasome activation that results in initiation, maturity and release of the pro-inflammatory cytokines and generation of reactive oxygen and nitrogen species. These components of the inflammatory response play important roles in many neural pathologies and neurodegeneration disorders. In CNS, expression of P2X7R on microglia, astrocytes, and oligodendrocytes are upregulated under neuroinflammatory conditions. Several in vivo studies have demonstrated beneficial effects of the P2X7 receptor antagonists in animal model systems of neurodegenerative diseases. A number of specific and selective P2X7 receptor antagonists have been developed, but only few of them have shown efficient brain permeability. Finding potent and selective P2X7 receptor inhibitors which are also CNS penetrable and display acceptable pharmacokinetics (PK) has presented challenges for both academic researchers and pharmaceutical companies. In this review, we discuss the role of P2X7 receptor function in neurodegenerative diseases, the pharmacological inhibition of the receptor, and PET radiopharmaceuticals which permit non-invasive monitoring of the P2X7 receptor contribution to neuroinflammation associated with neurodegeneration.
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Project description:The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles in leukemia are less clear and vary considerably among different types of leukemia. Some NRs participate in mediating the differentiation of myeloid cells, making them attractive therapeutic targets for myeloid leukemia. To date, the success of all-trans retinoic acid (ATRA) in treating acute promyelocytic leukemia (APL) remains a classical and unsurpassable example of cancer differentiation therapy. ATRA targets retinoic acid receptor (RAR) and forces differentiation and/or apoptosis of leukemic cells. In addition, ligands/agonists of vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) have also been shown to inhibit proliferation, induce differentiation, and promote apoptosis of leukemic cells. Encouragingly, combining different NR agonists or the addition of NR agonists to chemotherapies have shown some synergistic anti-leukemic effects. This review will summarize recent research findings and discuss the therapeutic potential of selected NRs in acute and chronic myeloid leukemia, focusing on RAR, VDR, PPAR, and retinoid X receptor (RXR). We believe that more mechanistic studies in this field will not only shed new lights on the roles of NRs in leukemia, but also further expand the clinical applications of existing therapeutic agents targeting NRs.
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Project description:The outbreak of coronaviruses (CoVs) presents an enormous threat to humans. To date, no new therapeutic drugs or vaccines licensed to treat human coronaviruses remain undiscovered. This mini-review briefly reports the number of potential plants widely distributed in Indonesia for further research and development as anti-SARS-CoV-2 agents and the critical targets for SARS-CoV-2 therapy, such as angiotensin-converting enzyme 2 (ACE-2) receptor, spike protein, 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), helicase, and serine protease. Indonesia is rich in medicinal plants (herbal); it also has a long history of using plants to treat various hereditary diseases. However, since SARS-CoV-2 is a new disease, it has no history of plant-based treatment anywhere in the world. This mini-review describes natural products from several Indonesian plants that contain compounds that could potentially prevent or reduce SARS-CoV-2 infection, act as potential targeted therapy, and provide new therapeutic strategies to develop SARS-CoV-2 countermeasures.
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