Curcumin: A small molecule with big functionality against amyloid aggregation in neurodegenerative diseases and type 2 diabetes

Radbakhsh, Shabnam; Barreto, George E.; Bland, Abigail R.; Sahebkar, Amirhossein

doi:10.1002/biof.1735

Cited by 31 publications

(19 citation statements)

References 131 publications

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“…Brazilin had a strong inhibitory effect on the aggregation of Aβ, remodeling Aβ amyloid fibrils by interaction with Aβ 17–42 pentamer [22] . In the past few decades, a subset of phenolic compounds, especially the polyphenols such as curcumin, myricetin, epigallocatechin gallate, hydroxycinnamic acids, rosmarinic acid, and ferulic acid, were reported to have strong anti‐aggregation effects on α‐Syn [26–36] . Interestingly, some compounds containing only one aromatic ring can inhibit α‐Syn aggregation [37] .…”

Section: Introductionmentioning

confidence: 99%

“…[22] In the past few decades, a subset of phenolic compounds, especially the polyphenols such as curcumin, myricetin, epigallocatechin gallate, hydroxycinnamic acids, rosmarinic acid, and ferulic acid, were reported to have strong anti-aggregation effects on α-Syn. [26][27][28][29][30][31][32][33][34][35][36] Interestingly, some compounds containing only one aromatic ring can inhibit α-Syn aggregation. [37] Due to the lack of structural information, the detailed mechanisms of α-Syn-phenolic compounds' interactions remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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Myricetin Inhibits α‐Synuclein Amyloid Aggregation by Delaying the Liquid‐to‐Solid Phase Transition

Chen

et al. 2022

ChemBioChem

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The aggregation of α-synuclein (α-Syn) is a critical pathological hallmark of Parkinson's disease (PD). Prevention of α-Syn aggregation has become a key strategy for treating PD. Recent studies have suggested that α-Syn undergoes liquid-liquid phase separation (LLPS) to facilitate nucleation and amyloid formation. Here, we examined the modulation of α-Syn aggregation by myricetin, a polyhydroxyflavonol compound, under the conditions of LLPS. Unexpectedly, neither the initial morphology nor the phase-separated fraction of α-Syn was altered by myricetin. However, the dynamics of α-Syn con-densates decreased upon myricetin binding. Further studies showed that myricetin dose-dependently inhibits amyloid aggregation in the condensates by delaying the liquid-to-solid phase transition. In addition, myricetin could disassemble the preformed α-Syn amyloid aggregates matured from the condensates. Together, our study shows that myricetin inhibits α-Syn amyloid aggregation in the condensates by retarding the liquid-to-solid phase transition and reveals that α-Syn phase transition can be targeted to inhibit amyloid aggregation. www.chembiochem.org

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myricetin Inhibits α‐Synuclein Amyloid Aggregation by Delaying the Liquid‐to‐Solid Phase Transition

Chen

et al. 2022

ChemBioChem

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“…Although these data need to be supported by additional studies showing a direct effect of curcumin on skin p-syn aggregates; the current experimental model supports a possible effect of curcumin on misfolded α-synuclein aggregates. In fact, curcumin directly binds to α-synuclein in vitro, and can both inhibit and reverse the formation of toxic α-synuclein aggregate species ( 17 , 19 , 20 ), thus promoting and stabilizing nonaggregate forms of α-syn ( 15 ). Curcumin may also improve the motor behavior of mice and binds Lewy bodies in human brain tissue ( 15 , 16 ).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

Nyholm

Incensi

Rizzo

et al. 2022

Journal of Neuropathology &Amp; Experimental Neurology

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There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

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“…Curcumin's ability to bind to Aβ-pleated structure reduces plaque stress in most AD plaque pathogenesis models (Yang et al, 2005;Garcia-Alloza et al, 2007;Cheng et al, 2013). Curcumin is also known for directly binding and inhibiting the aggregation of Aβ-sheet conformations found in many NDs (Cole et al, 2007;Mishra and Palanivelu, 2008;Forouzanfar et al, 2020;Radbakhsh et al, 2021).…”

Section: Curcumin and Neurodegenerative Diseases: Interventions And Modalitiesmentioning

confidence: 99%

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin

Mukherjee

Mishra

Peer

et al. 2021

Front. Aging Neurosci.

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Abnormal accumulation of misfolded proteins in the endoplasmic reticulum and their aggregation causes inflammation and endoplasmic reticulum stress. This promotes accumulation of toxic proteins in the body tissues especially brain leading to manifestation of neurodegenerative diseases. The studies suggest that deregulation of proteostasis, particularly aberrant unfolded protein response (UPR) signaling, may be a common morbific process in the development of neurodegeneration. Curcumin, the mixture of low molecular weight polyphenolic compounds from turmeric, Curcuma longa has shown promising response to prevents many diseases including current global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurodegenerative disorders. The UPR which correlates positively with neurodegenerative disorders were found affected by curcumin. In this review, we examine the evidence from many model systems illustrating how curcumin interacts with UPR and slows down the development of various neurodegenerative disorders (ND), e.g., Alzheimer’s and Parkinson’s diseases. The recent global increase in ND patients indicates that researchers and practitioners will need to develop a new pharmacological drug or treatment to manage and cure these neurodegenerative diseases.

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Curcumin: A small molecule with big functionality against amyloid aggregation in neurodegenerative diseases and type 2 diabetes

Cited by 31 publications

References 131 publications

Myricetin Inhibits α‐Synuclein Amyloid Aggregation by Delaying the Liquid‐to‐Solid Phase Transition

Myricetin Inhibits α‐Synuclein Amyloid Aggregation by Delaying the Liquid‐to‐Solid Phase Transition

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin

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