Proposal for novel curcumin derivatives as potent inhibitors against Alzheimer’s disease: Ab initio molecular simulations on the specific interactions between amyloid-beta peptide and curcumin

Ota, Shintaro; Fujimori, Mitsuki; Ishimura, Hiromi; Shulga, Sergiy; Kurita, Noriyuki

doi:10.1016/j.cplett.2017.08.024

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…Recently, novel curcumin derivatives were proposed as potent inhibitors against AD, e.g. protecting APP from secretase attacks, and consequently inhibiting the production of A peptides [136]. However, to date the anticipated benefits of curcumin have not been demonstrated in AD clinical trials [106].…”

Section: Curcuminmentioning

confidence: 99%

Mitigating Alzheimer’s Disease with Natural Polyphenols: A Review

Gaudreault

Mousseau

2019

CAR

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According to Alzheimer's Disease International (ADI), nearly 50 million people worldwide were living with dementia in 2017, and this number is expected to triple by 2050. Despite years of research in this field, the root cause and mechanisms responsible for Alzheimer's disease (AD) have not been fully elucidated yet.Moreover, promising preclinical results have repeatedly failed to translate into patient treatments. Until now, none of the molecules targeting AD has successfully passed the Phase III trial. Although natural molecules have been extensively studied, they normally require high concentrations to be effective; alternately, they are too large to cross the blood-brain barrier (BBB).In this review, we report on AD treatment strategies, with a virtually exclusive focus on green chemistry (natural phenolic molecules). These include therapeutic strategies for decreasing amyloid-(A ) production, preventing and/or altering A aggregation, and reducing oligomers cytotoxicity such as curcumin, (-)epigallocatechin-3-gallate (EGCG), morin, resveratrol, tannic acid, and other natural green molecules. We also examine whether consideration should be given to potential candidates used outside of medicine and nutrition, through a discussion of two intermediate-sized green molecules, with very similar molecular structures and key properties, which exhibit potential in mitigating Alzheimer's disease.

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Section: Curcuminmentioning

confidence: 99%

Mitigating Alzheimer’s Disease with Natural Polyphenols: A Review

Gaudreault

Mousseau

2019

CAR

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“…However, in another study conducted by molecular simulation on some curcumin derivatives, it was revealed that these compounds can bind to amyloid precursor protein (APP) at the cutoff site of ү-secretase, inhibiting the action of this enzyme and stopping the production of the insoluble peptide Aβ. 54,61,74 On the other hand, Orlando et al 58 studied the anti-Aβ activity in curcumin and 20 curcumin analogues. The authors propose three mechanisms by which curcumin can express anti-Aβ activity.…”

Section: Anti Aβ Activitymentioning

confidence: 99%

“…The second mechanism is the removal of Fe and Cu ions through binding the C‐O polar groups from the centre of the curcumin molecule to the metal ions in a chelation process. However, in another study conducted by molecular simulation on some curcumin derivatives, it was revealed that these compounds can bind to amyloid precursor protein (APP) at the cutoff site of ү‐secretase, inhibiting the action of this enzyme and stopping the production of the insoluble peptide Aβ 54,61,74 . On the other hand, Orlando et al 58 .…”

Section: Bioactive Compounds With Potential Biological Activity In Admentioning

confidence: 99%

Curcumin and omega‐3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease

Velasco‐Rodríguez,

García,

Rascón‐Díaz

2024

Psychogeriatrics

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Curcumin and omega‐3 polyunsaturated fatty acids (ω‐3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω‐3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω‐3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.

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“…The FMO method provides valuable information about the electronic properties of fragments and their molecular interactions. Recently, this method has been extensively used to study A β –ligand binding and stabilizing factors in small A β oligomers 30‐37 …”

Section: Introductionmentioning

confidence: 99%

Identification of key stabilizing interactions of amyloid‐β oligomers based on fragment molecular orbital calculations on macrocyclic β‐hairpin peptides

Firouzi

Noohi

2021

Proteins

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Analyzing the electronic states and inter‐/intra‐molecular interactions of amyloid oligomers expand our understanding of the molecular basis of Alzheimer's disease and other amyloid diseases. In the current study, several high‐resolution crystal structures of oligomeric assemblies of Aβ‐derived peptides have been studied by the ab initio fragment molecular orbital (FMO) method. The FMO method provides comprehensive details of the molecular interactions between the residues of the amyloid oligomers at the quantum mechanical level. Based on the calculations, two sequential aromatic residues (F19 and F20) and negatively charged E22 on the central region of Aβ have been identified as key residues in oligomer stabilization and potential interesting pharmacophores for preventing oligomer formation.

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Proposal for novel curcumin derivatives as potent inhibitors against Alzheimer’s disease: Ab initio molecular simulations on the specific interactions between amyloid-beta peptide and curcumin

Cited by 5 publications

References 24 publications

Mitigating Alzheimer’s Disease with Natural Polyphenols: A Review

Mitigating Alzheimer’s Disease with Natural Polyphenols: A Review

Curcumin and omega‐3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease

Identification of key stabilizing interactions of amyloid‐β oligomers based on fragment molecular orbital calculations on macrocyclic β‐hairpin peptides

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