Home Bratislava Medical Journal 2019 Bratislava Medical Journal Vol.120, No.2, p.148–154, 2019

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Published Monthly, in English
Founded: 1919
ISSN 0006-9248
(E)ISSN 1336-0345
 

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Bratislava Medical Journal Vol.120, No.2, p.148–154, 2019

Title: Investigation of THDOC effects on pathophysiological signs of Alzheimer’s disease as an endogenous neurosteroid: inhibition of acetylcholinesterase and plaque deposition
Author: H. Saleh, L. Sadeghi

Abstract: 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
Published online: 17-Feb-2019
Year: 2019, Volume: 120, Issue: 2 Page From: 148, Page To: 154
doi:10.4149/BLL_2019_024


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