Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy
Abstract
:1. Introduction
2. Molecular Mechanisms of Protein Deamidation
3. Role of Deamidation in Protein Aging
3.1. Deamidation and Neurodegenerative Diseases
3.2. Deamidated Proteins as a Biomarker
4. Protein Deamidation in Cancer
5. Protein Deamidation in Forensics and Archeology
6. Protein Deamidation in Biopharmaceuticals and Drug Development
7. Future Perspective
Funding
Data Availability Statement
Conflicts of Interest
References
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Sr No | Neurodegenerative Diseases | Deamidated Protein | Functional Consequences | References |
---|---|---|---|---|
1. | Alzheimer’s disease | Tau | Increased aggregation, reduced microtubule binding. | [72,73,74,75] |
Human serum albumin, neurofilament light protein (NfL), glial fibrillary acidic protein (GFAP) | Deamidation protein biomarkers for detection of neurodegeneration. | [76] | ||
Amyloid-beta (Aβ), Tau, Protein S100A9, 4E-BP2 Protein, Na+/K+-ATPase, Ion-Channel Proteins | Structural changes, functional inactivation, and enhanced aggregation. Impacts neurons and axons. | [12,28,29,56,77] | ||
2. | Parkinson’s disease | α-Synuclein, 4E-BP2 Protein | Aggregation, Impact neurons and axons. | [13,56] |
Ceruloplasmin | Ceruloplasmin in the CSF of PD patients undergoes conformational changes and NGR-motif deamidation, which promote the gain of integrin-binding function. Leads to loss of enzymatic activity, also confers gain of function to Cp. | [78,79] | ||
3. | Huntington’s disease | Huntingtin (HTT) | Abnormal conformation. | [80] |
4. | Amyotrophic lateral sclerosis | Superoxide dismutase | Structure destabilization, protein aggregation, toxic oligomer formation. | [81] |
5. | Prion diseases, Creutzfeldt-Jakob disease | Prion protein (PrP) | Change in conformation, misfolding. | [82] |
6. | Frontotemporal dementia | Tau, TDP-43 | Neuronal loss. | [74] |
7. | Spinocerebellar ataxia | Ataxin (varies by type) | Alter the protein’s stability, folding, and interactions. | |
8. | Multiple system atrophy | α-Synuclein | Misfolding and protein aggregation. | [83] |
9. | Progressive supranuclear palsy | Tau | Misfolding, aggregation, reduced microtubule binding, acceleration of NFT formation and disease progression. | [75,84] |
10. | Corticobasal degeneration | Tau | Misfolding, aggregation, reduced microtubule binding. | [75,84] |
11. | Cataract | α-Crystallin, β-crystallin, γ-crystallin | Altered structure, dimer formation, protein aggregation. | [31,62,85] |
12. | Lewy body dementia | α-Synuclein | Aggregation. | [13,86] |
13. | Vascular dementia | amyloid β peptides, Synapsin1, α-tubulin 1B (TUBA1B) and β-tubulin 2A (TUBB2A) proteins, human serum albumin, Na+/K+-ATPase, ion-channel proteins | Functional impairment and synaptic impairment. | [3,76,77,87,88] |
14. | Familial Alzheimer’s disease | Amyloid-beta (Aβ), Tau | Oligomerization/fibrillization, amyloid-related neurodegeneration. | [77,89] |
15 | Charcot–Marie–Tooth disease | Peripheral myelin proteins (PMP22) | Intracellular aggregation. | [90] |
16. | Niemann-Pick disease | Sphingomyelinase | Alterations in the function of the lysosomal system. | [91] |
17 | Diabetes (type 2 diabetes) | Amylin, islet amyloid polypeptide | Accelerates amyloid formation. | [92,93] |
18 | Alzheimer’s disease with tauopathy | Tau | Increased rates of β-sheet transition and fibril formation. | [94] |
19 | Gerstmann–Sträussler–Scheinker syndrome | Prion protein (PrP) | Aggregation and formation of PrP amyloid. Misfolding and pathogenicity of prion proteins. | [82,95] |
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Adav, S.S. Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy. Proteomes 2025, 13, 24. https://doi.org/10.3390/proteomes13020024
Adav SS. Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy. Proteomes. 2025; 13(2):24. https://doi.org/10.3390/proteomes13020024
Chicago/Turabian StyleAdav, Sunil S. 2025. "Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy" Proteomes 13, no. 2: 24. https://doi.org/10.3390/proteomes13020024
APA StyleAdav, S. S. (2025). Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy. Proteomes, 13(2), 24. https://doi.org/10.3390/proteomes13020024