Abstract
Alzheimer’s disease (AD) is a chronic neurodegenerative disorder. This study was designed to investigate the effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) on behavior, amyloid β (Aβ) plaque deposition, and βAPP cleaving enzyme-1 (BACE-1) expression in the 5xFAD mouse brain. In this study, computational studies were conducted to predict the binding mode of the 3NCP with target sites of the β-secretase. In vivo studies were performed on the 5xFAD mice model of AD using different behavioral test models like light/dark box, elevated plus maze (EPM), and the Barnes maze tests for the assessment of anxiety, spatial learning and memory. The thioflavin-S staining, immunohistochemistry (IHC), and RT-PCR studies were carried out to find the effect of the 3NCP on the β-amyloid plaques formation and BACE-1 expression. The results of the computational studies showed that the 3NCP has excellent binding affinities for beta-secretase. The light/dark box study depicted that the 3NCP does not cause anxiety. The 3NCP treatment effects in the EPM and Barnes maze tests showed a significant effect on learning and memory. Furthermore, the results of the thioflavin staining and IHC revealed that the 3NCP significantly reduced the formation of the beta-amyloid plaques in brain tissues. Moreover, the RT-PCR study showed that 3NCP significantly reduced the BACE-1 expression in the brain. Conclusively, the results of the current study demonstrate that the 3NCP may be a potential candidate for AD treatment in the future.
Highlights
Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder and affects memory-related brain areas [1]
HCregions regions of of the wild type of non‐transgenic mice treated with vehicle (A), FC and HC regions of the transgenic 5xFAD mice treated the wild type of non-transgenic mice treated with vehicle (A), FC and HC regions of the transgenic 5xFAD mice treated with vehicle (B), FC and HC regions of the 3NCP (10, 20, 40 mg/kg) treated 5xFAD mice (C–E), and the relative density of withAβ vehicle (B), FC and HC regions of the 3NCP (10, 20, 40 mg/kg) treated 5xFAD mice (C–E), and the relative density of plaques in FC (F) and HC (G)
There are many culprits involved in this destruction. One of these culprits is microscopic brain protein‐fragments known as beta‐amyloid that accumulate in the brain, disrupting communication between brain cells [30]
Summary
Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder and affects memory-related brain areas [1]. 1901, the German psychiatrist and neuropathologist Dr Alois Alzheimer described AD in a 51-year old patient named Auguste Deter who was suffering from chronic dementia and died in 1906 Her brain was analyzed by Alzheimer for the first time and he found extracellular tangles and intracellular plaques [3]. She was suffering from aphasia, memory impairment, hallucinations, psychosocial disorientation, and incompetence. At two months of age, they aggressively form the Amyloid beta plaques, with cognitive impairment occurring at four months of age, and neuronal loss cause at nine months [17,18] These animals exhibited APP plaques in different brain areas and increased Aβ1-40 and Aβ1-42 levels in the brain and cerebrospinal fluid. Attempts were made to examine the potential mechanisms of the neuroprotective effect of
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