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Etiology of oxidative stress behind Huntington’s disease (HD). In HD, reduced levels of ascorbate, cysteine, and antioxidants are observed. Excitatory amino acid transporter 3 (EAAT3/EAAC1) is the cysteine transporter, which is dysregulated and responsible for the reduced uptake of cysteine. Uptake of the oxidized form of cysteine is also reduced, which is mediated through the xCT and 4F2hc complex transporter. Sodium-dependent vitamin C transporters 2 (SVCT2)-mediated uptake of ascorbate (vitamin C), which is also reduced in HD, is responsible for the compromised antioxidant defense system in neurons. Cellular components are damaged because of metal deposition such as iron (Fe) and copper (Cu) in both cytoplasms and mitochondria, generating free radicals. Additional oxidative stress generates the mutant form of huntingtin aggregates (mHtt) in both the cytoplasm and nucleus. mHtt aggregates affect vital cellular processes such as mitochondrial dysfunction, proteostasis, and autophagy. In the nucleus, mHtt affects transcription factors involved in the cell’s antioxidant defense system. mHtt also affects DNA repair processes, which are responsible for damage and the error-prone repair system. Ascorbate (vitamin C) supplementation in HD improves the antioxidant defense system and prevents disease progression.
Source publication
Aquiring the recommended daily allowance of vitamins is crucial for maintaining homeo�static balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely
affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we
discuss how novel vitamin-based approaches aid in attenuating abno...
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Citations
... Deficits in cobalamin (B12), a cobalt-containing coordination molecule, can lead to megaloblastic anemia and neurological disorders. Water-soluble vitamins (WSVs) primarily serve as cofactors for associated enzymes, which allows them to modify the biological activity of enzymes [40,41]. Vitamin B12 serves as a crucial coenzyme in various chemical processes, including hydrogenation, dimerization, and dehalogenation. ...
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... Recent scientific investigations independently highlight the pivotal influence of vitamin B12 on various neurodegenerative processes. Its role in DNA synthesis, maintenance of neuronal myelin, cognitive health, vascular-mediated Aβ clearance, BBB integrity, protein aggregation pathways, and the modulation of microglial function is accentuated [9]. This wealth of insights contributes to a profound understanding of potential synergies between cannabinoids and vitamin B12 and highlight integrated therapeutic strategies. ...
... Further research and clinical validation are essential to unlock the full therapeutic potential of this integrated paradigm. Deficiencies in vitamin B12 have been linked to neurodegenerative disorders, with supplementation exhibiting potential in mitigating certain facets of cognitive decline [9]. Emerging evidence suggests that vitamin B12 may extend its influence beyond traditional roles, encompassing novel pathways that contribute to the neurodegenerative challenges. ...
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... Among its forms, alltrans retinoic acid (ATRA) is the most prevalent in cells [16]. Vitamin A deficiency in the CNS has been linked to cognitive diseases, including Alzheimer's and Parkinson's diseases, and autism spectrum disorder [17,18]. The specific impact of ATRA on tau pathology, however, remains underexplored. ...
This study investigates the role of all-trans retinoic acid (ATRA) in modulating the expression of heat shock protein 90 (Hsp90) and its influence on the uptake and degradation of tau proteins in immortalized human microglia cells. We demonstrate that ATRA significantly upregulates Hsp90 expression in a concentration-dependent manner, enhancing both extracellular and intracellular Hsp90 levels. Our results show that ATRA-treated cells exhibit increased tau protein uptake via caveolae/raft-dependent endocytosis pathways. This uptake is mediated by surface Hsp90, as evidenced by the inhibition of tau internalization using an extracellular Hsp90-selective inhibitor. Further, we establish that the exogenously added full-sized monomeric tau proteins bind to Hsp90. The study also reveals that ATRA-enhanced tau uptake is followed by effective degradation through both lysosomal and proteasomal pathways. We observed a significant reduction in intracellular tau levels in ATRA-treated cells, which was reversed by lysosome or proteasome inhibitors, suggesting the involvement of both degradation pathways. Our findings highlight the potential therapeutic role of ATRA in Alzheimer’s disease and related tauopathies. By enhancing Hsp90 expression and facilitating tau degradation, ATRA could contribute to the clearance of pathological tau proteins, offering a promising strategy for mitigating neurodegeneration. This research underscores the need for further exploration into the molecular mechanisms of tau protein internalization and degradation, which could provide valuable insights into the treatment of neurodegenerative diseases.
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... /fnut. . E levels between PD patients and controls, suggesting that serum vitamin E concentrations were not associated with the risk of PD (35)(36)(37). ...
Objective
Current evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years.
Methods
We conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD.
Results
According to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P < 0.05 for interaction).
Conclusion
Among participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.
... This is because vitamins commonly function as antioxidants or enzymatic cofactors [71,72]. A deficiency in, or a dysregulation of, specific vitamins adversely affects neuronal metabolism, which may lead to neurodegenerative diseases [73][74][75][76]. This prompted researchers to explore the role of different vitamins in the development and progression of diseases. ...
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Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to induce in-vitro models of Alzheimer disease to investigate the efficacy of different therapeutic drugs. We screened literature from databases such as PubMed, ScienceDirect, and Google scholar, emphasizing the diverse targeting mechanisms of neuro degeneration explored in in-vitro models. The results revealed studies in which different types of chemicals and environmental agents were used for in-vitro development of Alzheimer-targeting mechanisms of neurodegeneration. Studies using chemically induced in-vitro AD models included in this systematic review will contribute to a deeper understanding of AD. However, none of these models can reproduce all the characteristics of disease progression seen in the majority of Alzheimer’s disease subtypes. Additional modifications would be required to replicate the complex conditions of human AD in an exact manner. In-vitro models of Alzheimer’s disease developed using chemicals and environmental agents are instrumental in providing insights into the disease’s pathophysiology; therefore, chemical-induced in-vitro AD models will continue to play vital role in future AD research. This systematic screening revealed the pivotal role of chemical-induced in-vitro AD models in advancing our understanding of AD pathophysiology and is therefore important to understand the potential of these chemicals in AD pathogenesis.
