Role of Oxidative Stress and Metal Toxicity in the Progression of Alzheimer’s Disease

Birla, Hareram; Minocha, Tarun; Kumar, Gaurav; Misra, Anamika; Singh, Sandeep Kumar

doi:10.2174/1570159x18666200122122512

Cited by 46 publications

(38 citation statements)

References 125 publications

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“…Chen et al [11] found that the compound AB42chelated metals such as iron and copper and decreased metal-induced Aβ aggregation (Figure 3 and Table 2).…”

Section: Metal Accumulation and Metal Ion Dyshomeostasismentioning

confidence: 97%

“…In vitro In vivo can pass BBB [47] Monogalactose group inhibits Aβpeptide aggregation In vitro possibility to optimize the uptake across the BBB via the glucose transporter mechanism [11] The introduction of flexible moieties at the linker inhibit β-sheet aggregation and fibril formation…”

Section: Ref Modification Of Curcumin Actionmentioning

confidence: 99%

“…Chen et al [11] verified that AB42 can decrease or inhibit the β-sheet aggregation and the fibril formation (IC50= 2.5 μM and 90% inhibition at a concentration of 50 μM). A SAR analysis for all the synthesized analogues were performed, suggested that the introduction of flexible moieties at the The undertaken molecular docking studies of the curcumin derivatives describe the prerequesite structural characteristics for the exploration of the pharmacophore features of Aβ aggregation inhibition.…”

Section: In Vitromentioning

confidence: 99%

“…Furthermore, there are curcumin analogues and derivatives which were evaluated for their antioxidant activity in vitro. Chen et al [11] tested several compounds using the oxygen radical absorbance capacity assay using fluorescein (ORAC-FL). The absence of phenolic groups (methoxy or hydroxy) affected the antioxidant activity.…”

Section: Antioxidant Activitymentioning

confidence: 99%

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Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Chainoglou

Hadjipavlou‐Litina

2020

IJMS

102

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Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

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“…Chen et al [11] found that the compound AB42chelated metals such as iron and copper and decreased metal-induced Aβ aggregation (Figure 3 and Table 2).…”

Section: Metal Accumulation and Metal Ion Dyshomeostasismentioning

confidence: 97%

Section: Ref Modification Of Curcumin Actionmentioning

confidence: 99%

Section: In Vitromentioning

confidence: 99%

Section: Antioxidant Activitymentioning

confidence: 99%

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Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Chainoglou

Hadjipavlou‐Litina

2020

IJMS

102

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“…Increase in OS could be generated through the deregulation of metal homeostasis (Sayre et al, 2000 ), and there is evidence that metal-induced OS promotes Aβ deposition and tau pathology in AD (Greenough et al, 2013 ; Birla et al, 2020 ; Wang et al, 2020 ). At least partially, OS in AD has been linked to the impairment of copper homeostasis.…”

Section: Copper As An Os-inducer In Admentioning

confidence: 99%

The Role of Copper in Tau-Related Pathology in Alzheimer’s Disease

Zubčić

Hof

Šimić

et al. 2020

Front. Mol. Neurosci.

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All tauopathies, including Alzheimer’s disease (AD), are characterized by the intracellular accumulation of abnormal forms of tau protein in neurons and glial cells, which negatively affect microtubule stability. Under physiological conditions, tubulin-associated unit (Tau) protein is intrinsically disordered, almost without secondary structure, and is not prone to aggregation. In AD, it assembles, and forms paired helical filaments (PHFs) that further build-up neurofibrillary tangles (NFTs). Aggregates are composed of hyperphosphorylated tau protein that is more prone to aggregation. The pathology of AD is also linked to disturbed copper homeostasis, which promotes oxidative stress (OS). Copper imbalance is widely observed in AD patients. Deregulated copper ions may initiate and exacerbate tau hyperphosphorylation and formation of β-sheet-rich tau fibrils that ultimately contribute to synaptic failure, neuronal death, and cognitive decline observed in AD patients. The present review summarizes factors affecting the process of tau aggregation, conformational changes of small peptide sequences in the microtubule-binding domain required for these motifs to act as seeding sites in aggregation, and the role of copper in OS induction, tau hyperphosphorylation and tau assembly. A better understanding of the various factors that affect tau aggregation under OS conditions may reveal new targets and novel pharmacological approaches for the therapy of AD.

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Dihydromyricetin Improves Cognitive Impairments in d‐Galactose‐Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase

Sun

Yin

Chen

et al. 2021

Molecular Nutrition Food Res

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Scope Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d‐galactose (d‐gal) induced aging mice. Methods and Results Mice are intraperitoneally injected with d‐gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d‐gal‐induced cognitive impairments in novel object recognition and Y‐maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non‐competitive inhibitor of AChE with IC50 value of 161.2 µg mL−1. Conclusion DMY alleviates the cognitive impairments in d‐gal‐induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.

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Role of Oxidative Stress and Metal Toxicity in the Progression of Alzheimer’s Disease

Cited by 46 publications

References 125 publications

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

The Role of Copper in Tau-Related Pathology in Alzheimer’s Disease

Dihydromyricetin Improves Cognitive Impairments in d‐Galactose‐Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase

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