Journal of translational science
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Life expectancy of individuals in both developed and undeveloped nations continues to rise at an unprecedented rate. Coupled to this increase in longevity for individuals is the rise in the incidence of chronic neurodegenerative disorders that includes Alzheimer's disease (AD). Currently, almost ten percent of the population over the age of 65 suffers from AD, a disorder that is presently without definitive therapy to prevent the onset or progression of cognitive loss. ⋯ FoxOs play a critical role in determining survival of multiple cell types in the nervous system, drive pathways of apoptosis and autophagy, and control stem cell proliferation and differentiation. FoxOs also interface with multiple cellular pathways that include growth factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) that ultimately may control FoxOs and determine the fate and function of cells in the nervous system that control memory and cognition. Future work that can further elucidate the complex relationship FoxOs hold over cell fate and cognitive function could yield exciting prospects for the treatment of a number of neurodegenerative disorders including AD.
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Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. ⋯ Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI.
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Small non-coding ribonucleic acids (RNAs), known as microRNAs (miRNAs), are now becoming recognized as significant agents that can affect the onset and progression of numerous disorders throughout the body. In particular, miRNAs also may determine stem cell renewal and differentiation. ⋯ Targeting miRNAs that oversee SIRT1 activity offers interesting prospects for the translation of these pathways into efficacious clinical treatment programs for a host of disorders. Yet, as work in this area progresses, a number of challenges unfold that impact whether manipulation of non-coding RNAs and SIRT1 can finely guide stem cell renewal and differentiation to reach successful clinical outcomes.