β-Cyclodextrin and Curcumin, a Potent Cocktail for Disaggregating and/or Inhibiting Amyloids: A Case Study with α-Synuclein

Gautam, Saurabh; Karmakar, Sandip; Bose, Abhik; Chowdhury, P. K.

doi:10.1021/bi500642f

Cited by 47 publications

(39 citation statements)

References 15 publications

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“…As previously mentioned here for Aβ aggregation [125], the association of β-CD with curcumin was shown to increase the potency of the curcumin in inhibiting α-synuclein aggregation [81], and in dissolving preformed aggregates [82]. HPβCD conjugated to the agonist of dopamine receptor D3, D-264, enhanced its ability to cross the BBB compared to the parent molecule as observed in PD rat models in vivo and in vitro in the hybridoma dopaminergic MN9D cells [85].…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 66%

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Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE ® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer's, Parkinson's and Huntington's diseases are currently on-going.

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Section: Parkinson's Disease (Pd)mentioning

confidence: 66%

“…Nasal delivery system for L-DOPA into the brain [80] Increases curcumin potency in inhibiting α-synuclein aggregation [81], associated with curcumin Dissolves preformed α-synuclein aggregates [82], associated with curcumin…”

Section: Therapeutical Effect(s) Of Cds Referencementioning

confidence: 99%

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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“…Curcumin acts as scavenger of ROS, and it chelates iron and copper ions [200]. In a mixture with beta-cyclodextrin, it not only prevents the formation of the amyloid plaque but also disaggregates it [201].…”

Section: How To Prevent Neurodegeneration?-conclusion and Perspectivesmentioning

confidence: 99%

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

Pavlin

Repič²,

Vianello

et al. 2015

Mol Neurobiol

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We collected experimental kinetic rate constants for chemical processes responsible for the development and progress of neurodegeneration, focused on the enzymatic and non-enzymatic degradation of amine neurotransmitters and their reactive and neurotoxic metabolites. A gross scheme of neurodegeneration on the molecular level is based on two pathways. Firstly, reactive species oxidise heavy atom ions, which enhances the interaction with alpha-synuclein, thus promoting its folding to the beta form and giving rise to insoluble amyloid plaques. The latter prevents the function of vesicular transport leading to gradual neuronal death. In the second pathway, radical species, OH(·) in particular, react with the methylene groups of the apolar part of the lipid bilayer of either the cell or mitochondrial wall, resulting in membrane leakage followed by dyshomeostasis, loss of resting potential and neuron death. Unlike all other central neural system (CNS)-relevant biogenic amines, dopamine and noradrenaline are capable of a non-enzymatic auto-oxidative reaction, which produces hydrogen peroxide. This reaction is not limited to the mitochondrial membrane where scavenging enzymes, such as catalase, are located. On the other hand, dopamine and its metabolites, such as dopamine-o-quinone, dopaminechrome, 5,6-dihydroxyindole and indo-5,6-quinone, also interact directly with alpha-synuclein and reversibly inhibit plaque formation. We consider the role of the heavy metal ions, selected scavengers and scavenging enzymes, and discuss the relevance of certain foods and food supplements, including curcumin, garlic, N-acetyl cysteine, caffeine and red wine, as well as the long-term administration of non-steroid anti-inflammatory drugs and occasional tobacco smoking, that could all act toward preventing neurodegeneration. The current analysis can be employed in developing strategies for the prevention and treatment of neurodegeneration, and, hopefully, aid in the building of an overall kinetic molecular model of neurodegeneration itself.

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“…Small molecules such as curcumin are able to inhibit aSyn aggregation, [5,6] and more importantly,acocktail of curcumin and b-cyclodextrin has synergistic effects in inhibiting aggregation and promoting disaggregation of amyloids. [7] Cyclodextrins (CyDs) are aw ell-known family of cyclic oligosaccharides consisting of (1,4)-linked a-d-glucopyranose units. CyDsh ave shown ap otential role as antiaggregant and neuroprotective agents in pathologies relatedt ot he disruption of cholesterol homeostasis and amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

Cyclodextrins 3‐Functionalized with 8‐Hydroxyquinolines: Copper‐Binding Ability and Inhibition of Synuclein Aggregation

Oliveri

Sgarlata

Vecchio

2016

Chemistry An Asian Journal

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Neurodegenerative diseases such as Parkinson's and Alzheimer's diseases are multifactorial disorders related to protein aggregation, metal dyshomeostasis, and oxidative stress. To advance understanding in this area and to contribute to therapeutic development, many efforts have been directed at devising suitable agents that can target metal ions associated with relevant biomolecules such as α-synuclein. This paper presents a new cyclodextrin-8-hydroxyquinoline conjugate and discusses the properties of four cyclodextrins 3-functionalized with 8-hydroxyquinoline as copper(II) chelators and inhibitors of copper-induced synuclein aggregation. The encouraging results establish the potential of cyclodextrin-8-hydroxyquinoline conjugates as chelators for the control of copper toxicity.

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β-Cyclodextrin and Curcumin, a Potent Cocktail for Disaggregating and/or Inhibiting Amyloids: A Case Study with α-Synuclein

Cited by 47 publications

References 15 publications

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

Cyclodextrins 3‐Functionalized with 8‐Hydroxyquinolines: Copper‐Binding Ability and Inhibition of Synuclein Aggregation

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