Abstract
Since it has been shown that Alzheimer’s disease is accompanied by higher peripheral concentrations of cytokines, we focused on the correction of chronic inflammation causing Aβ excess and aggregation what should have a positive impact. Proinflammatory cytokines action is realized by NF-κB intracellular signals. Curcumin can inhibit activation of the proinflammatory transcription factor NF-κB and is able to be mounted in the amyloid-β fibrils and encourage their disaggregation. To study the influence of anti-inflammatory effect of curcumin and its ability to model complexes with a fragment of AβPP. Investigation was carried out on rats with model of Alzheimer’s disease using nasal therapy with curcumin Concentration of cytokines in cerebral cortex, hippocampus and blood serum, and indicators of conditioned active escape reflex were determined in this study. Methods of molecular dynamics and docking were used to examine the interactions of curcumin with fragment of AβPP. Аβ42_Human in the hippocampus of rats provoked chronic neuroinflammation specifically and primarily at the injection site. Curcumin performance revealed specific depressing effect on cytokines in the cerebral cortex and in the hippocampus it appeared similar to the above, but of lower level. Anti-inflammatory activity of curcumin led to the recovery of memory parameters. Analysis of restriction sites of AβPP has shown that position of curcumin in Site II is energetically more favorable for binding. Our suggestion that curcumin is an effective anti-cytokine factor was confirmed by experimental results obtained in vivo and explain the mechanism describing its effect on NF-κB Curcumin doesn’t block the excision Aβ but binding with its hydrophobic region.
Highlights
Aggregation of amyloid-β (Aβ) to form fibrils or depositions is considered to be one of the belivable factors of the pathology of Alzheimer's disease (AD), being the major pathogenetic event [1,2,3,4]
Processing within the non-amyloidogenic pathway involves full-length amyloid-β protein precursor (AβPP) cleaved by α- and γsecretases in the trans-Golgi network apparatus and plasma membrane, precluding amyloid-β formation
Since has previously been shown that AD is accompanied by an inflammatory response, higher peripheral concentrations of cytokines (IL-6, tumor necrosis factor-α (TNFα), IL-1β and other) and higher CSF concentrations of TGF-β [39], we focused on the correction of chronic inflammation that triggers Aβ excess and aggregation and should have a positive impact
Summary
Aggregation of amyloid-β (Aβ) to form fibrils or depositions is considered to be one of the belivable factors of the pathology of Alzheimer's disease (AD), being the major pathogenetic event [1,2,3,4]. Several studies have shown that Aβ accumulates abundantly in certain brain areas namely, hippocampus and cerebral cortex which subserve information acquisition and processing, and memory [5,6,7]. This peptide is formed within the amyloyidogenic processing of the amyloid-β protein precursor (AβPP) [8,9,10]. Processing within the non-amyloidogenic pathway involves full-length AβPP cleaved by α- and γsecretases in the trans-Golgi network apparatus and plasma membrane, precluding amyloid-β formation (or amyloidogenesis). Amyloid-β may be vital for the development of neurons, their plasticity and survival due to its integral membrane interactions, in maintaining the structural integrity of the blood brain barrier (BBB); it has antimicrobial properties and modulates intracellular Ca2+ transporting evoked by cholinergic receptors [26,27,28,29,30]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
