It is estimated that the prevalence rate of Alzheimer’s disease (AD) will double by the year 2040. Although currently available treatments help with symptom management, they do not prevent, delay the progression of, or cure the disease. Interestingly, a shared characteristic of AD and other neurodegenerative diseases and disorders is oxidative stress. Despite profound evidence supporting the role of oxidative stress in the pathogenesis and progression of AD, none of the currently available treatment options address oxidative stress. Recently, attention has been placed on the use of antioxidants to mitigate the effects of oxidative stress in the central nervous system. In preclinical studies utilizing cellular and animal models, natural antioxidants showed therapeutic promise when administered alone or in combination with other compounds. More recently, the concept of combination antioxidant therapy has been explored as a novel approach to preventing and treating neurodegenerative conditions that present with oxidative stress as a contributing factor. In this review, the relationship between oxidative stress and AD pathology and the neuroprotective role of natural antioxidants from natural sources are discussed. Additionally, the therapeutic potential of natural antioxidants as preventatives and/or treatment for AD is examined, with special attention paid to natural antioxidant combinations and conjugates that are currently being investigated in human clinical trials.
Although recent studies suggest homocysteine (Hcy) is an independent risk factor for neurodegenerative disorders, little is known about sex differences in the levels of Hcy. In this study, we conducted a comparative meta-analysis to investigate sex differences in the levels of Hcy in both Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients. Reports of Hcy stratified by sex in both AD and PD patients were obtained from electronic databases. From the initial 1595 records, 921 were assessed for eligibility, of which 16 sufficiently reported sex differences. Standardized mean difference (SMDs) using random effects together with tests of heterogeneity and quality assessment were applied in this meta-analysis. Data from 3082 diagnosed patients (1162 males and 1920 females) were included. There were statistically significant differences in the levels of Hcy between sexes in AD and PD patients, with an SMD of 0.291 [0.17, 0.41], p < 0.05, 95% CI, with higher Hcy levels detected in males. Subgroup comparisons did not find a statistically significant difference in the levels of Hcy between AD and PD patients. The overall risk of bias for the analyzed studies was low, with some moderate risk of bias across select domains. This meta-analysis determined that compared to females, males with either AD or PD have higher levels of Hcy. These findings suggest that Hcy could be a useful biomarker for predicting neurodegenerative diseases in males; however, further studies are needed to confirm the clinical utility of this suggestion.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that debilitates over 55 million individuals worldwide. Currently, treatments manage and alleviate its symptoms; however, there is still a need to find a therapy that prevents or halts disease progression. Since AD has been labeled as “type 3 diabetes” due to its similarity in pathological hallmarks, molecular pathways, and comorbidity with type 2 diabetes mellitus (T2DM), there is growing interest in using anti-diabetic drugs for its treatment. Rosiglitazone (RSG) is a peroxisome proliferator-activated receptor-gamma agonist that reduces hyperglycemia and hyperinsulinemia and improves insulin signaling. In cellular and rodent models of T2DM-associated cognitive decline and AD, RSG has been reported to improve cognitive impairment and reverse AD-like pathology; however, results from human clinical trials remain consistently unsuccessful. RSG has also been reported to modulate the expression of brain-derived neurotrophic factor (BDNF), a protein that regulates neuroplasticity and energy homeostasis and is implicated in both AD and T2DM. The present review investigates RSG’s limitations and potential therapeutic benefits in pre-clinical models of AD through its modulation of BDNF expression.
Antioxidants are being explored as novel therapeutics for the treatment of neurodegenerative diseases such as Alzheimer’s disease (AD) through strategies such as chemically linking antioxidants to synthesize novel co-drugs. The main objective of this study was to assess the cytoprotective effects of the novel antioxidant compound VANL-100 in a cellular model of beta-amyloid (Aβ)-induced toxicity. The cytotoxic effects of Aβ in the presence and absence of all antioxidant compounds were measured using the 3-(4,5-dimethylthiazol-2-yl)2-5-diphenyl-2H-tetrazolium bromide (MTT) assay in SH-SY5Y cells in both pre-treatment and co-treatment experiments. In pre-treatment experiments, VANL-100, or one of its parent compounds, naringenin (NAR), alpha-lipoic acid (ALA), or naringenin + alpha-lipoic acid (NAR + ALA), was administrated 24 h prior to an additional 24-h incubation with 20 μM non-fibril or fibril Aβ25–35. Co-treatment experiments consisted of simultaneous treatment with Aβ and antioxidants. Pre-treatment and co-treatment with VANL-100 significantly attenuated Aβ-induced cell death. There were no significant differences between the protective effects of VANL-100, NAR, ALA, and NAR + ALA with either form of Aβ, or in the effect of VANL-100 between 24-h pre-treatment and co-treatment. These results demonstrate that the novel co-drug VANL-100 is capable of eliciting cytoprotective effects against Aβ-induced toxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.