111 research outputs found
Impacting dementia and cognitive loss with innovative strategies: mechanistic target of rapamycin, clock genes, circular non-coding ribonucleic acids, and Rho/Rock
No full textNovel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease
No full textDiabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4) to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus
Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR
No full textThroughout the globe, diabetes mellitus (DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), AMP activated protein kinase (AMPK), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), Wnt1 inducible signaling pathway protein 1 (WISP1), and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM
Free Radical–Mediated Damage to Brain in Alzheimer’s Disease: Role of Acrolein and Preclinical Promise of Antioxidant Polyphenols
No full textBrain aging is associated with accumulation of oxidation-induced damage, likely due to the imbalance between antioxidant defenses and intracellular generation of reactive oxygen species (ROS). Alzheimer’s disease (AD) is the most frequent neurodegenerative disease with multiple causes, and aging is considered as the major risk factor for the development of this disease. From early stages, oxidative damage is strongly implicated in the pathophysiology of this disorder. Lipid peroxidation generates various by-products such as F2α-isoprostane, 4-hydroxynonenal, malondialdehyde, and acrolein with the latter being the most reactive. In the neuroblastoma SK-N-SH cell line, our results show that acrolein can induce cell toxicity through a nonapoptotic pathway. Moreover, acrolein can alter the redox state by depleting glutathione levels. Considering the role of oxidative stress and the toxic effect of by-products of lipid oxidation, intake of compounds with antioxidant activities such as polyphenolic compounds may be beneficial in the prevention of AD. In this chapter, we will review the role of free radical–mediated damage in AD and in transgenic mouse models and present the main intracellular target of polyphenolic compounds underlying their potential neuroprotective effect.</br
Correction to: Epistemic Challenges in Neurophenomenology: Exploring the Reliability of Knowledge and Its Ontological Implications (Philosophies, (2023), 8, 5, (94), 10.3390/philosophies8050094)
No full textThe author would like to make the following corrections to the published paper [1]. The changes are as follows: Affiliation change:Department of Philosophy, Ural Federal University, 620002 Ekaterinburg, Russia. Name correction of the philosopher Michelle Maiese in Section 2 “Theoretical Framework”. Affiliation change: Department of Philosophy, Ural Federal University, 620002 Ekaterinburg, Russia. Name correction of the philosopher Michelle Maiese in Section 2 “Theoretical Framework”. Original text: Michelle Maze presents an argument that challenges the traditional separation between cognitive and bodily aspects of emotions [49] (p. 514). Maze suggests that understanding emotions as a means of interacting with and giving meaning to the external world can help bridge this divide. Maze introduces the concept of affective framing as a foundational basis for emotional experiences. According to Maze, affective framing involves the evaluation of the environment through bodily sensations of care, which leads to the merging of cognitive and bodily elements in emotions. This concept not only clarifies the relationship between the cognitive and bodily aspects of emotions but also offers a valuable framework for understanding the intentional focus and phenomenal nature of emotional experiences. Updated text: Michelle Maiese presents an argument that challenges the traditional separation between cognitive and bodily aspects of emotions [49] (p. 514). Maiese suggests that understanding emotions as a means of interacting with and giving meaning to the external world can help bridge this divide. Maiese introduces the concept of affective framing as a foundational basis for emotional experiences. According to Maiese, affective framing involves the evaluation of the environment through bodily sensations of care, which leads to the merging of cognitive and bodily elements in emotions. This concept not only clarifies the relationship between the cognitive and bodily aspects of emotions but also offers a valuable framework for understanding the intentional focus and phenomenal nature of emotional experiences. Adding an Acknowledgment section. Acknowledgments: AI-assisted tools were used in the preparation (translation of the article into English) of the article. © 2024 by the author
Neuronal and vascular plasticity elucidating basic cellular mechanisms for future therapeutic discovery
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