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Alzheimer's disease (AD) is considered to be the most typical form of dementia that provokes irreversible cognitive impairment. Along with cognitive impairment, circadian rhythm dysfunction is a fundamental factor in aggravating AD. A link among circadian rhythms, sleep, and AD has been well‐documented. The etiopathogenesis of circadian system disruptions and AD serves some general characteristics that also open up the possibility of viewing them as a mutually reliant path. In this review, we have focused on different factors that are related to circadian rhythm dysfunction. The various pathogenic factors, such as amyloid‐beta, neurofibrillary tangles, oxidative stress, neuroinflammation, and circadian rhythm dysfunction may all contribute to AD. In this review, we also tried to focus on melatonin which is produced from the pineal gland and can be used to treat circadian dysfunction in AD. Aside from amyloid beta, tau pathology may have a notable influence on sleep. Conclusively, the center of this review is primarily based on the principal mechanistic complexities associated with circadian rhythm disruption, sleep deprivation, and AD, and it also emphasizes the potential therapeutic strategies to treat and prevent the progression of AD. [ABSTRACT FROM AUTHOR]

Because of the complex cascade of molecular events that can occur in the brain of an Alzheimer''s disease (AD) patient, the therapy of this neurodegenerative disease seems more likely to be achieved by multifunctional drugs. Herein, a new series of dual-targeting ligands have been developed and in vitro bioevaluated. Their architecture is based on conjugating the acetylcholinesterase inhibition and anti-oxidant properties in one molecular entity. Specifically, a series of naturally occurring phenolic acids with recognized anti-oxidant properties (derivatives of caffeic acid, rosmarinic acid, and trolox) have been conjugated with choline to account for the recognition by acetylcholinesterase (AChE). The synthesized hybrid compounds evidenced AChE inhibitory capacity of micromolar range (rationalized by molecular modeling studies) and good antioxidant properties. Their effects on human neuroblastoma cells, previously treated with beta-amyloid peptides and 1-methyl-4-phenylpyridinium ion neurotoxins (to simulate AD and Parkinson''s disease, respectively), also demonstrated a considerable capacity for protection against the cytotoxicity of these stressors. [ABSTRACT FROM AUTHOR]

Objectives: Estrogen is known to prominently benefit neuronal syndromes and neurodegenerative diseases. Ginsenoside Rg1, an active ingredient found in a Chinese plant, ginseng root, was previously demonstrated to exert estrogen-like activity. This study was performed to assess the neuroprotective effect of ginsenoside Rg1 against apoptosis induced by ββ-amyloid protein 25--35 (Aββ25--35) in primary cultured rat hippocampal neuronal cells as well as in the underlying mechanisms. Methods: We first measured cell viability and lactate dehydrogenase (LDH) release from primary cultured rat hippocampal neurons. After that, the inhibition effects of ginsenoside Rg1 on neuronal cell apoptosis were evaluated with flow cytometric analysis. Furthermore, western blot analysis was used for detecting the expression of apoptosis-related proteins Bcl-2, Bax, and active caspase 3. Results: The results show that ginsenoside Rg1 could increase neuronal viability and reduce LDH release; rescue cell apoptosis induced by Aββ25--35; decrease the expression of caspase 3, increase the ratio of Bcl-2/Bax at the protein levels compared with the cells only treated with Aββ25--35. Conclusions: Taken together, our results indicate that the apoptosis induced by Aββ25--35 could be reversed by ginsenoside Rg1. Furthermore, this neuroprotective effect is probably mediated by up-regulating the ratio of Bcl-2/Bax that activates caspase 3. [ABSTRACT FROM AUTHOR]

Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In this article, recent progress in the application of solid-state NMR to fibrils associated with Alzheimer's disease, prion fibrils, and related systems is reviewed, along with relevant developments in solid-state NMR techniques and technology. [ABSTRACT FROM AUTHOR]

Current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. Solid-state nuclear magnetic resonance (NMR) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. In this article, recent progress in the application of solid-state NMR to fibrils associated with Alzheimer's disease, prion fibrils, and related systems is reviewed, along with relevant developments in solid-state NMR techniques and technology. [ABSTRACT FROM AUTHOR]