Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration

Nakamura, Tomohiro; Oh, Chang-ki; Zhang, Xu; Lipton, Stuart A.

doi:10.1016/j.freeradbiomed.2021.07.002

Cited by 51 publications

(29 citation statements)

References 224 publications

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“…Post-translational modifications of amyloidogenic proteins, as a rule, weaken their binding to chaperones [ 87 , 135 , 136 ], which prevents their blocking effect on the chaperone system. One of the main mechanisms for the accumulation of modified misfolded proteins in the brain in pathological disorders is exposure to reactive oxygen species (ROS) and reactive nitrogen species (RNS) [ 137 ]. It should be noted that RNS modify proteins not only by S-nitrosylation of their sulfhydryl groups.…”

Section: Blocking Of Chaperones By Misfolded Proteins and Amyloidogen...mentioning

confidence: 99%

“…For example, the modification of small heat shock proteins, causing the formation of cross-linked oligomeric forms, reduces their anti-aggregation activity [ 139 ]. Complex ATP-dependent chaperones are particularly sensitive to such modifications [ 137 ]. The chaperonin Hsp90 can be nitrated at tyrosine residues, which induces nerve cell death [ 140 ].…”

Section: Post-translational Modifications and Functioning Of Chaperonesmentioning

confidence: 99%

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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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Section: Blocking Of Chaperones By Misfolded Proteins and Amyloidogen...mentioning

confidence: 99%

Section: Post-translational Modifications and Functioning Of Chaperonesmentioning

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

View full text Add to dashboard Cite

show abstract

“…Abnormally oxidized tissue content of misfolded proteins increased with age. [14] The available drugs for PD are chemically active converted into dopamine or dopamine agonists in the brain that may inhibit dopamine metabolism. Patients using these medications have several side effects, such as nausea and headache.…”

Section: Introductionmentioning

confidence: 99%

“…With age, various chaperones cannot induce polyubiquitination, causing the accumulation of such misfolded proteins and eventually forming lewy bodies. Abnormally oxidized tissue content of misfolded proteins increased with age [14] …”

Section: Introductionmentioning

confidence: 99%

Identification of alpha‐Synuclein Disaggregator from Camellia sp. Insight of Molecular Docking and Molecular Dynamics Simulations

2022

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Misfolded protein formation and aggregation are the central hallmarks for various neurodegenerative disorders. When it comes to Parkinson's disease (PD), alpha-synuclein (α-syn) is the culprit protein. The presence of α-syn protein in lewy bodies and lewy neurites confirmed its presence in the occurrence of PD. The protein is natively present in the soluble monomeric forms, but certain factors such as oxidative stress convert the structure into insoluble oligomeric formats. This study focuses on the inhibitory effects of various antioxidant compounds on α-syn oligomerization. We had collected the list of compounds present in the Camellia sp. plant. Using a computational approach, we found the potential interaction sites between the antioxidant compounds and α-syn using a computational approach. Molecular docking and simulation studies suggest that the compound Theaflavin-3-3-digallate shows best interactions with À 7.1 kcal/mol and can reduce the alpha-sheet structure of α-syn structure to loop region.

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“…NO and NO-derived species (e.g., N 2 O 3 , NO + ) can directly react with thiol groups in proteins or in sulfhydryl-containing low molecular weight molecules, such as glutathione, free cysteine, and Coenzyme A (CoA). Otherwise, Snitroso (SNO) groups can be generated via transnitrosylation, the transfer of an NO moiety between thiols and S-nitrosothiols (thiol/nitrosothiol exchange) (Nakamura et al, 2021). This mechanism is also the basis of protein denitrosylation, which is the process required to remove NO from S-nitrosothiols and regenerate protein thiol pools.…”

mentioning

confidence: 99%

Nitric oxide-based regulation of metabolism: Hints from TRAP1 and SIRT3 crosstalk

Faienza

Rasola

Filomeni

2022

Front. Mol. Biosci.

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Nitric oxide in metabolism regulationNitric oxide (NO) is a gaseous signaling molecule able to modify protein structure and activity (Rizza and Filomeni, 2017). The addition of the NO moiety to a cysteine thiol is called S-nitrosylation, which is establishing as one of the major NO-induced protein posttranslational modifications involved in cell signaling (Fernando et al., 2019). In the presence of oxygen-and reactive oxygen species (ROS), mostly superoxide (O 2 -)-NO can also give rise to other biologically active compounds, such as peroxynitrite (ONOO − ) (Fernando et al., 2019). Peroxynitrite is highly reactive and commonly recognized being detrimental to macromolecules, as it can cause irreversible modifications to lipids (peroxidation) and proteins (tyrosine nitration) (Radi, 2018). Nitric oxide is endogenously generated by nitric oxide synthases (NOSs), a family of three isozymes (neuronal, endothelial, and inducible) whose subcellular localization and activation influence NO target selectivity (Benhar et al., 2009). NO and NO-derived species (e.g., N 2 O 3 , NO + ) can directly react with thiol groups in proteins or in sulfhydryl-containing low molecular weight molecules, such as glutathione, free cysteine, and Coenzyme A (CoA). Otherwise, Snitroso (SNO) groups can be generated via transnitrosylation, the transfer of an NO moiety between thiols and S-nitrosothiols (thiol/nitrosothiol exchange) (Nakamura et al., 2021). This mechanism is also the basis of protein denitrosylation, which is the process required to remove NO from S-nitrosothiols and regenerate protein thiol pools. Three are the denitrosylases so far characterized: i) S-nitrosoglutathione reductase (GSNOR); ii) S-nitroso-CoA reductase (ScoR) and iii) thioredoxin reductase (TrxR). All these enzymes do not directly react with S-nitrosylated proteins, but specifically recognize, and remove, the NO moiety from small S-nitrosothiols (S-nitrosoglutathione, S-nitroso-CoA and thioredoxin, respectively) generated by transnitrosylation with S-nitrosylated proteins (Rizza and Filomeni, 2017).

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Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration

Cited by 51 publications

References 224 publications

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

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

Identification of alpha‐Synuclein Disaggregator from Camellia sp. Insight of Molecular Docking and Molecular Dynamics Simulations

Nitric oxide-based regulation of metabolism: Hints from TRAP1 and SIRT3 crosstalk

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