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Sulfur-containing therapeutics in the treatment of Alzheimer's disease.

ABSTRACT: Sulfur is widely existent in natural products and synthetic organic compounds as organosulfur, which are often associated with a multitude of biological activities. OBenzothiazole, in which benzene ring is fused to the 4,5-positions of the thiazolerganosulfur compounds continue to garner increasing amounts of attention in the field of medicinal chemistry, especially in the development of therapeutic agents for Alzheimer's disease (AD). AD is a fatal neurodegenerative disease and the primary cause of age-related dementia posing severe societal and economic burdens. Unfortunately, there is no cure for AD. A lot of research has been conducted on sulfur-containing compounds in the context of AD due to their innate antioxidant potential and some are currently being evaluated in clinical trials. In this review, we have described emerging trends in the field, particularly the concept of multi-targeting and formulation of disease-modifying strategies. SAR, pharmacological targets, in vitro/vivo ADMET, efficacy in AD animal models, and applications in clinical trials of such sulfur compounds have also been discussed. This article provides a comprehensive review of organosulfur-based AD therapeutic agents and provides insights into their future development.

SUBMITTER: Zhu H

PROVIDER: S-EPMC7889054 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionWith the pressing need to develop treatments that slow or stop the progression of Alzheimer's disease, new tools are needed to reduce clinical trial duration and validate new targets for human therapeutics. Such tools could be derived from neurophysiological measurements of disease.Methods and analysisThe New Therapeutics in Alzheimer's Disease study (NTAD) aims to identify a biomarker set from magneto/electroencephalography that is sensitive to disease and progression over 1 year. The study will recruit 100 people with amyloid-positive mild cognitive impairment or early-stage Alzheimer's disease and 30 healthy controls aged between 50 and 85 years. Measurements of the clinical, cognitive and imaging data (magnetoencephalography, electroencephalography and MRI) of all participants will be taken at baseline. These measurements will be repeated after approximately 1 year on participants with Alzheimer's disease or mild cognitive impairment, and clinical and cognitive assessment of these participants will be repeated again after approximately 2 years. To assess reliability of magneto/electroencephalographic changes, a subset of 30 participants with mild cognitive impairment or early-stage Alzheimer's disease will also undergo repeat magneto/electroencephalography 2 weeks after baseline. Baseline and longitudinal changes in neurophysiology are the primary analyses of interest. Additional outputs will include atrophy and cognitive change and estimated numbers needed to treat each arm of simulated clinical trials of a future disease-modifying therapy.Ethics and data statementThe study has received a favourable opinion from the East of England Cambridge Central Research Ethics Committee (REC reference 18/EE/0042). Results will be disseminated through internal reports, peer-reviewed scientific journals, conference presentations, website publication, submission to regulatory authorities and other publications. Data will be made available via the Dementias Platform UK Data Portal on completion of initial analyses by the NTAD study group.

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Sulfur-containing therapeutics in the treatment of Alzheimer's disease.

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