Mcfaddengleason1657

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Alzheimer's Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes. OBJECTIVES Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity. METHODS In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine. RESULTS Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 µM) and AChE (33.21 µM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 µM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests. CONCLUSION Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.The molecular processes underlying neurodegenerative diseases (such as Alzheimer's Disease - AD) remain poorly understood. There is also an imperative need for disease-modifying therapies in AD since the present treatments, acetylcholinesterase inhibitors and NMDA antagonists, do not halt its progression. AD and other dementias present unique pathological features such as that of microtubule associated protein tau metabolic regulation. Tau has numerous binding partners, including signaling molecules, cytoskeletal elements and lipids, which suggests that it is a multifunctional protein. AD has also been associated with severe loss of cholinergic markers in the brain and such loss may be due to the toxic interaction of tau with cholinergic muscarinic receptors. By using specific antagonists of muscarinic receptors it was found in vitro that extracellular tau binds to M1 and M3 receptors and which the increase of intracellular calcium found in neuronal cells upon tau-binding. However, so far, the significance of tau signaling through muscarinic receptor in vivo in tauopathic models remains uncertain. learn more The data reviewed in the present paper highlight the significant effect of M1 receptor/tau interaction in exacerbating tauopathy related pathological features and suggest that selective M1 agonists may serve as a prototype for future therapeutic development toward modification of currently intractable neurodegenerative diseases, such as tauopathies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.Prader-Willi syndrome (PWS) is an imprinted neurodevelopmental disease characterized by cognitive impairments, developmental delay, hyperphagia, obesity, and sleep abnormalities. It's caused by lack of expression of the paternally active genes in the PWS imprinting center on chromosome 15 (15q11.2-q13). Owing to the imprinted gene regulation, the same genes in the maternal chromosome 15q11-q13 are intact in structure but repressed at the transcriptional level because of the epigenetic mechanism. The specific molecular defect underlying PWS provides an opportunity to explore epigenetic therapy to reactivate the expression of repressed PWS genes inherited from the maternal chromosome. The purpose of this review is to summarize the main advances in the molecular study of PWS and discuss current and future perspectives on the development of CRISPR/Cas9-mediated epigenome editing in the epigenetic therapy of PWS. Twelve studies on molecular mechanism or epigenetic therapy of PWS were included in the review. Although our understanding of the molecular basis of PWS has changed fundamentally, there have been little progress in the epigenetic therapy of PWS that targets its underlying genetic defects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.This review is focused on the healing of fistulas and stable gastric pentadecapeptide BPC 157. Assuming that the healing of the various wounds is essential also for the gastrointestinal fistulas healing, the healing effect on fistulas in rats, consistently noted with the stable gastric pentadecapeptide BPC 157, may raise several interesting possibilities. BPC 157 is originally an anti-ulcer agent, native to and stable in human gastric juice (for more than 24 h). Likely, it is a novel mediator of Robert's cytoprotection maintaining gastrointestinal mucosal integrity. Namely, it is effective in the whole gastrointestinal tract, and heals various wounds (i.e., skin, muscle, tendon, ligament, bone; ulcers in the entire gastrointestinal tract; corneal ulcer); LD1 is not achieved. It is used in ulcerative colitis clinical trials, and now in multiple sclerosis, and addressed in several reviews. Therefore, it is not surprising that BPC 157 has documented consistent healing of the various gastrointestinal fistulas, external (esophagocutaneous, gastrocutaneous, duodenocutaneous, colocutaneous) and internal (colovesical, rectovaginal). Taking fistulas as a pathological connection, this rescue is verified with the beneficial effects in rats with the various gastrointestinal anastomoses, esophagogastric, jejunoileal, colo-colonic, ileoileal, esophagojejunal, esophagoduodenal, and gastrojejunal. This beneficial effect occurs equally when the gastrointestinal anastomoses are impaired with the application of NSAIDs, cysteamine, large bowel resection, as well as concomitant esophageal, gastric, and duodenal lesions and/or ulcerative colitis presentation, short bowel syndrome progression, liver and brain disturbances presentation. Particular aspects of the BPC 157 healing of the fistulas are especially emphasized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.