Chapters authored
The Mystery of P2X7 Ionotropic Receptor: From a Small Conductance Channel to a Large Conductance Channel
Part of the book: Neuroscience
The Role of Purinergic Signaling in the Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy
Perinatal hypoxic-ischemic encephalopathy (HIE), known as birth asphyxia, remains a major contributor to poor neurodevelopmental outcomes including cerebral palsy and seizures. One striking feature of HIE injury is a delayed progression of neuronal degeneration that spreads over time from the most severely damaged areas outward into neighboring undamaged regions. There is increasing evidence that these lesions act as sites of origin for waves of spreading depression (SD), a wave of neuronal and glial depolarization, that progressively enlarge the brain lesions. While the pathophysiology of SD is still under debate, there is increasing evidence that purinergic receptors in conjunction with connexin and pannexin 1 channels are necessary for sustained propagation of the waves and neuroinflammation. This review intends to discuss the relative contribution of purinergic signaling and connexin and pannexin 1 channels to trigger and spread SD waves leading to the development of progressive brain lesions under conditions of perinatal HIE.
Part of the book: Receptors P1 and P2 as Targets for Drug Therapy in Humans
A Brief View of Molecular Modeling Approaches to P2 Receptors
Purinergic receptors are a class of receptors distributed into two groups, P1 and P2. P1 receptors are activated by nucleosides, like adenosine, while nucleotides active P2 receptors. In turn, P2 receptors comprise two families, metabotropic P2Y and ionotropic P2X. P2Y receptors consist in eight members, namely, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14, described in mammals, while P2X includes seven members, numbered P2X1 to P2X7. These receptors have been described as expressed in practically all cells studied to date. In this context, P2 receptors are suggested as participating in certain diseases. The general approach applied in the discovery of new drugs is expensive and lengthy. Alternatively, in the last 20 years, molecular modeling has emerged as an exciting tool for the design of new drugs, in less time and at low costs. These tools allow for in silico testing of thousands of molecules against a target protein, as well as toxicity, absorption, distribution, metabolism, and constant affinity predictions of a given interaction. Thus, molecular modeling algorithms emerge as an increasingly important tool for the design of drugs targeting purinergic receptors as therapeutic targets of many diseases, including cancer, pain, inflammation, cardiovascular, and endocrine conditions.
Part of the book: Receptors P1 and P2 as Targets for Drug Therapy in Humans
Sonodynamic and Photodynamics Used as a Combined Therapy in the Treatment of Malignant Neoplasms: Facts and Open Questions
Photodynamic therapy (PDT) used in combination with sonodynamic therapy (SDT) is a new approach that aims to increase the effectiveness of tumor treatment when compared to the effect of each independent therapy. PDT is based on stimulating sensitizers with photons, while the most accepted theory for SDT is that sensitizers are stimulated by the sonoluminescence phenomenon. However, after the excitation of the sensitizer, both therapies follow a common path, leading to the generation of free radicals and inducing cell death. One of the positive aspects of this combination is the augmentation of anti-tumor activity with fewer side effects, since cell death may be induced using lower sensitizer concentrations or less exposure to ultrasound or light. Another benefit of combining PDT and SDT, especially with the use of low-frequency ultrasound is the induction of sonophoresis. For instance, on the skin, it may facilitate the absorption of the sensitizer. However, research involving both PDT and SDT exhibit many variants, including differences in irradiation sources and their intensities, among others. These aspects contribute to a lack of standardization, leading to result variations, hindering assessment on the real contribution that these combined therapies can offer in tumor treatment. Thus, further research in the pre-clinical and clinical areas are crucial.
Part of the book: Photodynamic Therapy