Curcumin Interacts with α-Synuclein Condensates To Inhibit Amyloid Aggregation under Phase Separation

Xu, Bingkuan; Chen, Jing; Liu, Yinghui

doi:10.1021/acsomega.2c03534

Cited by 34 publications

(27 citation statements)

References 81 publications

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“…The anti-amyloidogenic properties of polyphenols may also benefit Parkinson’s neurodegeneration, since the deposition of Lewy bodies, consisting of a large part of α-synuclein aggregates, in neuron cytoplasm is a key pathological PD hallmark [ 126 ]. In fact, the progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, together with iron accumulation, provides dopamine depletion in the striatum, thus neuromelanin disappear and Lewy bodies become visible.…”

Section: Polyphenols Vs Neurodegenerative Diseasementioning

confidence: 99%

Neuro-Nutraceutical Polyphenols: How Far Are We?

et al. 2023

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The brain, composed of billions of neurons, is a complex network of interacting dynamical systems controlling all body functions. Neurons are the building blocks of the nervous system and their impairment of their functions could result in neurodegenerative disorders. Accumulating evidence shows an increase of brain-affecting disorders, still today characterized by poor therapeutic options. There is a strong urgency to find new alternative strategies to prevent progressive neuronal loss. Polyphenols, a wide family of plant compounds with an equally wide range of biological activities, are suitable candidates to counteract chronic degenerative disease in the central nervous system. Herein, we will review their role in human healthcare and highlight their: antioxidant activities in reactive oxygen species-producing neurodegenerative pathologies; putative role as anti-acetylcholinesterase inhibitors; and protective activity in Alzheimer’s disease by preventing Aβ aggregation and tau hyperphosphorylation. Moreover, the pathology of these multifactorial diseases is also characterized by metal dyshomeostasis, specifically copper (Cu), zinc (Zn), and iron (Fe), most important for cellular function. In this scenario, polyphenols’ action as natural chelators is also discussed. Furthermore, the critical importance of the role exerted by polyphenols on microbiota is assumed, since there is a growing body of evidence for the role of the intestinal microbiota in the gut–brain axis, giving new opportunities to study molecular mechanisms and to find novel strategies in neurological diseases.

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Section: Polyphenols Vs Neurodegenerative Diseasementioning

confidence: 99%

Neuro-Nutraceutical Polyphenols: How Far Are We?

et al. 2023

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“…It is worth mentioning that some polyphenols, such as myricetin and curcumin, have been recently described to inhibit α-Syn liquid-to-solid transition in LLPS condensates. Adding these polyphenols to the condensates did not impact their morphology, but they increased the protein solubility, preventing amyloid transition and disentangling the preformed aggregates [ 253 , 254 ]. Structure–Activity Relationship (SAR) analysis of multiple phenolic variants with inhibitory activity revealed that the phenyl group alone does not prevent fibril formation [ 255 ].…”

Section: New Therapies: Modulating α-Synuclein Aggregationmentioning

confidence: 99%

Development of Small Molecules Targeting α-Synuclein Aggregation: A Promising Strategy to Treat Parkinson’s Disease

2023

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Parkinson’s disease, the second most common neurodegenerative disorder worldwide, is characterized by the accumulation of protein deposits in the dopaminergic neurons. These deposits are primarily composed of aggregated forms of α-Synuclein (α-Syn). Despite the extensive research on this disease, only symptomatic treatments are currently available. However, in recent years, several compounds, mainly of an aromatic character, targeting α-Syn self-assembly and amyloid formation have been identified. These compounds, discovered by different approaches, are chemically diverse and exhibit a plethora of mechanisms of action. This work aims to provide a historical overview of the physiopathology and molecular aspects associated with Parkinson’s disease and the current trends in small compound development to target α-Syn aggregation. Although these molecules are still under development, they constitute an important step toward discovering effective anti-aggregational therapies for Parkinson’s disease.

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“…This interaction with condensates reduces the diffusion of the protein, which ensures the inhibition of the formation of aggregates. Curcumin has also been shown to inhibit not only wild-type (WT) amyloids, but also α-synuclein mutant E46K and H50Q amyloids in condensates, making it a potential treatment for PD [ 139 ]. In addition to the above, there is an alternative hypothesis about the mechanism of inhibition of amyloid aggregation, which consists of inhibiting the generation of oxidative stress, increasing reduced glutathione, and preventing a glial-associated inflammatory response [ 140 ].…”

Section: Influence Of Various Molecules On the Aggregation Processmentioning

confidence: 99%

The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation

Galzitskaya

Grishin

Glyakina

et al. 2023

IJMS

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In recent years, due to the aging of the population and the development of diagnostic medicine, the number of identified diseases associated with the accumulation of amyloid proteins has increased. Some of these proteins are known to cause a number of degenerative diseases in humans, such as amyloid-beta (Aβ) in Alzheimer’s disease (AD), α-synuclein in Parkinson’s disease (PD), and insulin and its analogues in insulin-derived amyloidosis. In this regard, it is important to develop strategies for the search and development of effective inhibitors of amyloid formation. Many studies have been carried out aimed at elucidating the mechanisms of amyloid aggregation of proteins and peptides. This review focuses on three amyloidogenic peptides and proteins—Aβ, α-synuclein, and insulin—for which we will consider amyloid fibril formation mechanisms and analyze existing and prospective strategies for the development of effective and non-toxic inhibitors of amyloid formation. The development of non-toxic inhibitors of amyloid will allow them to be used more effectively for the treatment of diseases associated with amyloid.

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Curcumin Interacts with α-Synuclein Condensates To Inhibit Amyloid Aggregation under Phase Separation

Cited by 34 publications

References 81 publications

Neuro-Nutraceutical Polyphenols: How Far Are We?

Neuro-Nutraceutical Polyphenols: How Far Are We?

Development of Small Molecules Targeting α-Synuclein Aggregation: A Promising Strategy to Treat Parkinson’s Disease

The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation

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