Molecular mechanism of prion‐like tau‐induced neurodegeneration
Abstract
Introduction: Accumulation of hyperphosphorylated tau and the disruption of microtubules are correlated with synaptic loss and pathology of Alzheimer's disease (AD). Impaired cognitive function and pathology of AD is correlated with this lesion. This review looks at the mechanism of neurodegeneration, the prion‐like behavior of tau in its interaction with normal MAPs in correlation with tau hyperphosphorylation. Methods: We reviewed our work in the field as well as current literature that pertains to tau phosphorylation and the biological effects. Results: Hyperphosphorylation of tau in AD, in vitro, in cells, or in animal models converts this protein into a prion‐like protein that is able to propagate the altered conformation. Discussion: These findings suggest that phosphorylation of tau is a critical event in neurodegeneration. The combination of phosphorylation sites can generate a gain of toxic function for tau. The mechanism of tau toxicity might involve not only the microtubule system but also interference with other cellular compartments such as the nucleus and the actin cytoskeleton.
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Abnormally hyperphosphorylated or oligomeric tau can be secreted from neurons into the extracellular space, taken up by other normal neurons, and cause interneuronal transfer of tau pathology and spreading of tau toxicity across different brain regions.
“there is a large amount of evidence indicating that the abnormally hyperphosphorylated or oligomeric tau can be secreted from neurons into the extracellular space, then be taken up by other normal neurons, and finally causes interneuronal transfer of tau pathology and spreading of tau toxicity across different brain regions [59–61]”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [59]
Different conformations of tau protein in the human body can cause tau protein lesions with different symptoms, and these different conformations resemble prion strains.
“Different conformations of tau protein in the human body can cause tau protein lesions with different symptoms, and these different conformations resemble “prion strains”.”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [21]
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- Authors
- Alonso, A. D., Beharry, C., Corbo, C. P., & Cohen, L. S.
- Affiliations
- College of Staten Island (US)
- Wagner College (US)
- Corresponding author
- Alonso, Alejandra D.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-04-25
- Volume
- 12
- Issue
- 10
- Pages
- 1090-1097
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2345286701
- Cited by
- 53
- References
- 75
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 10
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association (IIRG‐09‐133206)
- 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 hyperphosphorylation, prion-like behavior
- MeSH terms
- Alzheimer Disease, Animals, Humans, Microtubules, Phosphorylation, tau Proteins, Prion Diseases, Tauopathies
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