Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies

Zheng, Qingyuan; Kebede, Micheal T.; Kemeh, Merc M.; Islam, Saadman; Lee, Bethany; Bleck, Stuart D.; Wurfl, Liliana A; Lazo, Noel D.

doi:10.3390/molecules24122316

Cited by 58 publications

(39 citation statements)

References 119 publications

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“…In turn, the Aβ peptides are a source of the reactive ROS and RNS free radicals, the excessive accumulation of which leading eventually to the neuronal disintegration. Polyphenols, because of their antioxidant property, sequester the ROS and RNS, and thereby prevent the formation of toxic Aβ oligomers and modulate tau-protein hyperphosphorylation, thereby preventing the formation of the neurofibrillary tangles (NFTs) [29].…”

Section: Oxidative Stress In the Formation Of The Aβ Protein Aggregatesmentioning

confidence: 99%

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

et al. 2020

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Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

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Section: Oxidative Stress In the Formation Of The Aβ Protein Aggregatesmentioning

confidence: 99%

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

et al. 2020

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“…Many phytochemicals inhibit mTOR signaling, thereby inducing the autophagy pathway [ 6 , 79 ]. Polyphenols inhibit oligomer synthesis and formation, in addition to preventing tau hyperphosphorylation and aggregation reduction under in vitro and in vivo conditions [ 80 ]. Soluble Aβ oligomers along with profibrillar species are produced via the action of rosmarinic acid, myricetin, and curcumin, which reduce the number of toxic oligomers and fibrils [ 81 , 82 ].…”

Section: Phytochemicals Prevent Mitochondrial Dysfunction and Imprmentioning

confidence: 99%

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

Rahman

Biswas³

et al. 2020

Antioxidants

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial or nuclear DNA that encode mitochondrial components may cause mitochondrial dysfunction. In particular, the dysfunction of electron transport chain complexes, along with the interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunction in AD. Mitochondrial dysfunction causes an imbalance in the production of reactive oxygen species, leading to oxidative stress (OS) and vice versa. Neuroinflammation is another potential contributory factor that induces mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense systems, thereby protecting against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Therefore, pharmacological intervention via neuroprotective phytochemicals can be a potential strategy to combat mitochondrial dysfunction as well as AD. This review focuses on the role of phytochemicals in mitigating mitochondrial dysfunction in the pathogenesis of AD.

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“…Many phytochemicals have been found to inhibit mTOR signaling, thereby inducing autophagy pathway [6,72]. Polyphenols have also been revealed to inhibit oligomer synthesis and formation in addition to prevent tau hyperphosphorylation and aggregation reduction in vitro and in vivo [73]. Soluble Aβ oligomers along with profibrillar species are produced via the action of rosmarinic acid, myricetin, and curcumin which reduced the toxic oligomers as well as fibrils [74,75].…”

Section: Phytochemicals Inhibit Ad Specific Protein Aggregationmentioning

confidence: 99%

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

Rahman¹,

Rahman²,

Biswas³

et al. 2020

Preprint

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function with neuronal damage. Although the precise pathobiology of AD is still elusive, accumulating evidences suggest that mitochondrial dysfunction is one of the underlying causes of AD. Mutations of mitochondrial or nuclear DNA that encode mitochondrial constituents may cause mitochondrial dysfunctions. In particular, dysfunction of electron transport chain complexes along with interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunctions in AD. Mitochondrial dysfunction causes an imbalance in reactive oxygen species, leading to oxidative stress (OS) and vice-versa. Neuroinflammation is another potential contributory factor to induce mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense system, and thereby protect against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Pharmacological intervention through neuroprotective phytochemicals can, therefore, be a potential strategy to combat mitochondrial dysfunctions as well as AD. This review focuses on the role of phytochemicals to mitigate mitochondrial dysfunction in the therapy of AD pathogenesis.

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Inhibition of the Self-Assembly of Aβ and of Tau by Polyphenols: Mechanistic Studies

Cited by 58 publications

References 119 publications

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

Polyphenols in Alzheimer’s Disease and in the Gut–Brain Axis

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

Potential Therapeutic Role of Phytochemicals to Mitigate Mitochondrial Dysfunctions in Alzheimer’s Disease

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