We have located links that may give you full text access.
Investigation of THDOC effects on pathophysiological signs of Alzheimer's disease as an endogenous neurosteroid: inhibition of acetylcholinesterase and plaque deposition.
Alzheimer's disease (AD) is an advanced neurodegenerative disorder greatly accompanied by acetylcholinesterase (AChE) activation and amyloid plaque deposition. Tetrahydrodeoxycorticosterone (THDOC) is an endogenous neurosteroid that is reduced in AD patient according to previous results. It has neuroprotective effects and plays important role in neurological diseases. By considering AChE role in AD, this study investigated THDOC effects on catalytic and non-catalytic functions of the enzyme. Inhibitory effect of THDOC on hydrolytic activity of AChE was confirmed by in vitro assay (IC50 = 5.68 µM). Molecular docking analysis revealed THDOC bound tightly to the catalytic site of enzyme and inhibited substrate binding. According to in vivo experiments, neurosteroid administration causes inhibition of hyper-activated AChE in hippocampus related to rat model of AD. Staining of hippocampus tissue by plaque specific dye approved THDOC reduced plaque numbers and size in AD rats. Histological and immunoblotting experiments showed neurosteroid administration improved neurodegeneration and neuronal damages in AD rats that lead to improved spatial learning ability. Overall this study suggests, THDOC is an endogenous regulator for AChE. By considering pathophysiological and molecular similarities between AD and animal model, our results highlight THDOC as a potential therapeutic strategy in patients suffering from AD or similar cognitive disorders (Fig. 6, Ref. 28). Keywords: tetrahydrodeoxycorticosterone, acetylcholinesterase, non-catalytic function, amyloid plaque deposition, nucleus basalis of Meynert lesioned rats, neurodegeneration.
Full text links
Trending Papers
A Personalized Approach to the Management of Congestion in Acute Heart Failure.Heart International 2023
Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium-Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure.International Journal of Molecular Sciences 2024 Februrary 21
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app