Current neurovascular research
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Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction. ⋯ SIRT1 interfaces with a number of pathways that involve forkhead transcription factors, mechanistic of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Wnt1 inducible signaling pathway protein 1 (WISP1) such that the level of activity of SIRT1 can become a critical determinant for biological and clinical outcomes. The essential fine control of SIRT1 is directly tied to the world of non-coding RNAs that ultimately oversee SIRT1 activity to either extend or end cellular survival. Future studies that can further elucidate the crosstalk between SIRT1 and non-coding RNAs should serve well our ability to harness the power of SIRT1 and non-coding RNAs for the treatment of vascular disorders.
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Review
Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin.
Transient receptor potential (TRP) channels are a superfamily of ion channels termed after the trp gene in Drosophila that are diverse in structure and control a wide range of biological functions including cell development and growth, thermal regulation, and vascular physiology. Of significant interest is the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including capsaicin and camphor, venoms, acid/basic pH changes, and temperature. ⋯ TRPV1 receptors could prove to become vital to target disorders of vascular origin and neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1 receptors can be envisioned for for the development of novel therapeutic strategies in multiple systems of the body.
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With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. ⋯ Given the ability of FoxOs to not only promote apoptotic cell death in the nervous system, but also through the induction of autophagy offer protection against degenerative disease that can lead to dementia, a fine balance in the activity of FoxOs may be required to target cognitive loss in individuals. Future work should yield exciting new prospects for FoxO proteins as new targets to treat the onset and progression of cognitive loss and dementia.
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Ununited peripheral nerves represent attractive site for connectivity with neuroprostheses because their predictable internal topography allows precise sorting of motor and sensory signals. Also transplantation of bone marrow mesenchymal stem cells (BMSCs) is increasingly recognized as an effective method of restore the peripheral nervous system injury due to its neuron-directed differentiation potential. This study was to evaluate the in vivo performance of BMSCs-packed Poly(3,4-ethylenedioxythiophene) (PEDOT) scaffolds across a critical nerve conduction gap and examine the potential mechanism by which BMSCs-packed PEDOT scaffolds mediate peripheral nerve regeneration in rat model of recurrent laryngeal nerve (RLN) deletion. ⋯ Meanwhile, both miR-21 overexpression and Notch pathway activation promote the expression of 6 nerve cell markers in BMSCs-directed neuron, whereas the inactivation of Notch pathway abrogates miR-21-inudced upregulation of 6 nerve cell markers. Moreover, knock-down of miR-21 suppresses the pro-neural restoration action of BMSCs-packed PEDOT scaffolds. In summary, our data suggested that BMSCs-packed PEDOT effectively repairs recurrent laryngeal nerve injury and the potential mechanism is miR-21- mediated Notch signal activation.
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The mammalian circadian clock and its associated clock genes are increasingly been recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. ⋯ Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.