Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes.

Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. Adv Pharmacol. 2017;79:117-139 Authors: Rajasekhar P, Poole DP, Veldhuis NA Abstract Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability th...
Source: Advances in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Adv Pharmacol Source Type: research

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Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Peter W. Stacpoole, Christopher J. Martyniuk, Margaret O. James, Nigel A. CalcuttAbstractDichloroacetate (DCA) has been the focus of research by both environmental toxicologists and biomedical scientists for over 50 years. As a product of water chlorination and a metabolite of certain industrial chemicals, DCA is ubiquitous in our biosphere at low μg/kg body weight daily exposure levels without obvious adverse effects in humans. As an investigational drug for numerous congenital and acquired diseases, DCA is administered orally or p...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Krish Chandrasekaran, Muragundla Anjaneyulu, Joungil Choi, Pranith Kumar, Mohammad Salimian, Cheng-Ying Ho, James W. RussellAbstractSurvival of human peripheral nervous system neurons and associated distal axons is highly dependent on energy. Diabetes invokes a maladaptation in glucose and lipid energy metabolism in adult sensory neurons, axons and Schwann cells. Mitochondrial (Mt) dysfunction has been implicated as an etiological factor in failure of energy homeostasis that results in a low intrinsic aerobic capacity within the neuron...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Amy E. Rumora, Masha G. Savelieff, Stacey A. Sakowski, Eva L. FeldmanAbstractPeripheral neuropathy is a common and debilitating complication of diabetes and prediabetes. Recent clinical studies have identified an association between the development of neuropathy and dyslipidemia in prediabetic and diabetic patients. Despite the prevalence of this complication, studies identifying molecular mechanisms that underlie neuropathy progression in prediabetes or diabetes are limited. However, dysfunctional mitochondrial pathways in hereditary ...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Annalisa Trecarichi, Sarah J.L. FlattersAbstractSeveral first-line chemotherapeutic agents, including taxanes, platinum agents and proteasome inhibitors, are associated with the dose-limiting side effect of chemotherapy-induced peripheral neuropathy (CIPN). CIPN predominantly manifests as sensory symptoms, which are likely due to drug accumulation within peripheral nervous tissues rather than the central nervous system. No treatment is currently available to prevent or reverse CIPN. The causal mechanisms underlying CIPN are not yet ful...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Ricardo H. Roda, Ahmet HokeAbstractMitochondria play an essential role in cellular energy production and calcium homeostasis. Abnormalities in mitochondrial homeostasis and function are seen in several acquired as well as genetic neuropathies, emphasizing their prominent role in neuronal cell activities. Chronic infection with HIV, even when appropriately treated, is a risk factor for developing peripheral neuropathy. In this chapter, we discuss the way in which HIV infection, the resultant toxic viral products that are generated, and ...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 145Author(s): Robert E. SchmidtAbstractThis is a new, exciting time for the study of peripheral nerve and its diseases. For many years research in peripheral neuropathies largely involved descriptive analysis, a situation which is now rapidly giving way to hypothesis testing with the development and validation of molecular genetic tools. Although it has been known for some time that many neuropathies target the most distal portions of the longest peripheral nerves, a process variously referred to as central-peripheral distal neuropathy, “dying...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
According to the International Diabetes Federation (IDF), diabetes mellitus (DM) affects 415 million people worldwide, with a prevalence of 8.8%, and these values are expected to rise still further, to 642 million by the year 2040, with a prevalence of 10.4% [1]. One of the most frequent complications of DM is diabetic peripheral neuropathy (DPN). In 2005, the American Diabetes Association (ADA) defined DPN as “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes, after the exclusion of other causes” [2].
Source: Primary Care Diabetes - Category: Primary Care Authors: Tags: Original research Source Type: research
CONCLUSIONS: The results of this study demonstrated that skin hydration in the feet of patients with diabetes mellitus mainly is influenced by microcirculation rather than peripheral nerve function. PMID: 31184593 [PubMed - as supplied by publisher]
Source: Wounds - Category: General Medicine Tags: Wounds Source Type: research
Conclusion: Physicians should discuss with the patients the different options outlining potential benefit and toxicity since no clear evidence of an approach of choice can be produced.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Publication date: Available online 11 June 2019Source: International Review of NeurobiologyAuthor(s): Peter W. Stacpoole, Christopher J. Martyniuk, Margaret O. James, Nigel A. CalcuttAbstractDichloroacetate (DCA) has been the focus of research by both environmental toxicologists and biomedical scientists for over 50 years. As a product of water chlorination and a metabolite of certain industrial chemicals, DCA is ubiquitous in our biosphere at low μg/kg body weight daily exposure levels without obvious adverse effects in humans. As an investigational drug for numerous congenital and acquired diseases, DCA is administere...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
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