Post-translational modifications of tau protein in Alzheimer’s disease
Abstract
Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal post-translational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.
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Tau undergoes several post-translational modifications that influence its function, aggregation and toxicity.
“Tau undergoes several post-translational modifications that influence its function, aggregation and toxicity73.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [73]
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- Authors
- Gong, C.-X., Liu, F., Grundke-Iqbal, I., & Iqbal, K.
- ORCID
- Venue
- Journal of Neural Transmission
- Published
- 2004-10-27
- Volume
- 112
- Issue
- 6
- Pages
- 813-838
- ISSN
- 0300-9564 (ISSN-L)
- 1435-1463
- OpenAlex
- W2023193162
- Cited by
- 437
- References
- 14
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 18 · 2023: 16 · 2022: 26 · 2021: 17 · 2020: 30 · 2019: 19 · 2018: 28 · 2017: 20 · 2016: 12 · 2015: 15 · 2014: 14 · 2013: 26 · 2012: 21
- FWCI
- 12.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG19158, R01AG019158, AG16760, R01AG016760)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, post-translational modification, Alzheimer's disease, tau hyperphosphorylation, paired helical filaments, neurofibrillary degeneration, tauopathy, ubiquitination, nitration, proteolysis, cerebrospinal fluid biomarkers, tau aggregation, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Glycosylation, Humans, Phosphorylation, Protein Processing, Post-Translational, Biomarkers, tau Proteins
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