Alpha-Synuclein Amyloid Aggregation Is Inhibited by Sulfated Aromatic Polymers and Pyridinium Polycation

Semenyuk, Pavel I.; Kurochkina, Lidia P.; Barinova, Kseniya; Muronetz, Vladimir I.

doi:10.3390/polym12030517

Cited by 17 publications

(18 citation statements)

References 50 publications

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“…The compounds were also non-toxic towards human neuroblastoma cell line making them very promising for treating synucleinopathies [57]. In a recent study, Medvedeva et al reported the ability of 3-methoxy-4-hydroxycinnamic acid (64), 3,4-dimethoxycinnamic acid (66) and 3-methoxy-4-acetamidoxycinnamic acid (82) (Figure 20) [57] to prevent alpha-synuclein amyloid transformation, thus aiding the treatment of Parkinson's disease [58]. The IC50 values of the compounds were 251 µM for 64, 50 µM for 82 and 13 µM for 2.…”

Section: Cinnamic Acid Derivatives With Neurological Activitymentioning

confidence: 99%

Cinnamic Acid Derivatives and Their Biological Efficacy

Ruwizhi

Aderibigbe

2020

IJMS

280

134

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The role played by cinnamic acid derivatives in treating cancer, bacterial infections, diabetes and neurological disorders, among many, has been reported. Cinnamic acid is obtained from cinnamon bark. Its structure is composed of a benzene ring, an alkene double bond and an acrylic acid functional group making it possible to modify the aforementioned functionalities with a variety of compounds resulting in bioactive agents with enhanced efficacy. The nature of the substituents incorporated into cinnamic acid has been found to play a huge role in either enhancing or decreasing the biological efficacy of the synthesized cinnamic acid derivatives. Some of the derivatives have been reported to be more effective when compared to the standard drugs used to treat chronic or infectious diseases in vitro, thus making them very promising therapeutic agents. Compound 20 displayed potent anti-TB activity, compound 27 exhibited significant antibacterial activity on S. aureus strain of bacteria and compounds with potent antimalarial activity are 35a, 35g, 35i, 36i, and 36b. Furthermore, compounds 43d, 44o, 55g–55p, 59e, 59g displayed potent anticancer activity and compounds 86f–h were active against both hAChE and hBuChE. This review will expound on the recent advances on cinnamic acid derivatives and their biological efficacy.

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Section: Cinnamic Acid Derivatives With Neurological Activitymentioning

confidence: 99%

Cinnamic Acid Derivatives and Their Biological Efficacy

Ruwizhi

Aderibigbe

2020

IJMS

280

134

View full text Add to dashboard Cite

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“…Moreover, certain types of cationic dendrimers bind to monomeric forms of sheep prion [ 22 , 23 ] or beta-amyloid peptide [ 24 ], which prevents their further amyloid aggregation. Sulfated aromatic polymers inhibit the formation of alpha-synuclein fibrils in vitro [ 25 ], while sulfated polysaccharides inhibit the accumulation of amyloid aggregates of the prion protein in cell culture [ 26 ]. However, on the contrary, many polymeric molecules interacting with amyloidogenic proteins stimulate their pathological transformation.…”

Section: Effect Of Artificial Chaperones On the Pathological Transfor...mentioning

confidence: 99%

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

Muronetz

Kudryavtseva

Leisi

et al. 2022

IJMS

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The review highlights various aspects of the influence of chaperones on amyloid proteins associated with the development of neurodegenerative diseases and includes studies conducted in our laboratory. Different sections of the article are devoted to the role of chaperones in the pathological transformation of alpha-synuclein and the prion protein. Information about the interaction of the chaperonins GroE and TRiC as well as polymer-based artificial chaperones with amyloidogenic proteins is summarized. Particular attention is paid to the effect of blocking chaperones by misfolded and amyloidogenic proteins. It was noted that the accumulation of functionally inactive chaperones blocked by misfolded proteins might cause the formation of amyloid aggregates and prevent the disassembly of fibrillar structures. Moreover, the blocking of chaperones by various forms of amyloid proteins might lead to pathological changes in the vital activity of cells due to the impaired folding of newly synthesized proteins and their subsequent processing. The final section of the article discusses both the little data on the role of gut microbiota in the propagation of synucleinopathies and prion diseases and the possible involvement of the bacterial chaperone GroE in these processes.

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“…Kinetic of α-Syn bril formation was assessed in presence of 0 and 500 µM of each metal ion using ThT uorescence assay 41,42 . ThT uorescence assays were carried on a Cary Eclipse VARIAN uorescence spectrophotometer (Mulgrave, Australia).…”

Section: Thio Avin T Uorescence Assaymentioning

confidence: 99%

Various metal ions promote formation of α-Synuclein fibrils with different shapes and cytotoxicities.

Saboury

Atarod

Mamashli

et al. 2022

Preprint

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α-Synuclein (α-Syn) aggregates are key components of intracellular inclusion bodies characteristic of Parkinson’s disease (PD) and other synucleinopathies. Metal ions have been considered as the important etiological factors in PD since their interactions with α-Syn alter the kinetics of fibrillation. In the present study, we have systematically explored the effects of Zn2+, Cu2+, Ca2+, and Mg2+ cations on α-Syn fibril formation. Specifically, we determined fibrillation kinetics, size, morphology, and secondary structure of the fibrils and their cytotoxic activity. While all cations accelerate fibrillation we observed distinct effects of the different ions. For example, Zn2+ induced fibrillation by lower tlag and higher kapp and formation of shorter fibrils, while Ca2+ ions lead to formation of longer fibrils, evidences by dynamic light scattering and atomic force microscopy studies. Additionally, the morphology of formed fibrils was different. Circular dichroism studies revealed higher content of antiparallel β-sheets in fibrils formed in the presence of Zn2+. Interestingly, cell viability studies indicated nontoxicity of α-Syn fibrils formed in the presence of Zn2+ ions, while the fibrils formed in the presence of Cu2+, Ca2+, and Mg2+ were cytotoxic. Our results revealed that α-Syn fibrils formed in the presence of different divalent cations have distinct structural and cytotoxic features and indicate a protective role of Zn2+ in the formation of neurotoxic α-Syn assemblies.

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Alpha-Synuclein Amyloid Aggregation Is Inhibited by Sulfated Aromatic Polymers and Pyridinium Polycation

Cited by 17 publications

References 50 publications

Cinnamic Acid Derivatives and Their Biological Efficacy

Cinnamic Acid Derivatives and Their Biological Efficacy

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

Various metal ions promote formation of α-Synuclein fibrils with different shapes and cytotoxicities.

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