Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases
Open accessAbstract
Organization of cytoskeletal elements is critical for cellular migration and maintenance of morphology. Tau protein, which binds to and organizes microtubules, is instrumental in forming and maintaining the neuronal axon. Disturbances in tau expression result in disruption of the neuronal cytoskeleton and formation of pathological tau structures (neurofibrillary tangles, NFTs) found in brains of dementia sufferers. Null tau mice, although viable, exhibit developmental and cognitive defects and transgenic mice which overexpress tau develop severe neuropathies. The neuron-specific tau transcript produces multiple isoforms by intricately regulated alternative splicing. These isoforms modulate tau function in normal brain. Moreover, aberrations in tau splicing regulation directly cause several neurodegenerative diseases. Thus, tau splicing regulation is vital to neuronal health and correct brain function. This review briefly presents our cumulative knowledge of tau splicing-cis elements and trans factors which influence it at the RNA level, its effect on the structure and roles of the tau protein and its repercussions on neuronal morphology and neurodegeneration.
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Adult brain-specific splicing of MAPT and SCN2A is seen exclusively in iNs and adult brain, whereas iPSC-iNs predominantly express the fetal isoforms.
“In addition, adult brain-specific splicing of the microtubule-associated protein tau (MAPT) (Andreadis, 2005) and of the voltage-gated sodium channel gene SCN2A (Sanders et al., 2018) was seen exclusively in iNs and adult brain, whereas iPSC-iNs predominantly expressed the fetal isoforms (Figure S7).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Andreadis, 2005
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Evolution of neuronal and glial tau isoforms in chronic traumatic encephalopathy
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Self-citationTwo sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia
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Expression of embryonic tau protein isoforms persist during adult neurogenesis in the hippocampus
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Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1
Leroy, O., Wang, J., Maurage, C., Parent, M., Cooper, T. A., Buée, L., Sergeant, N., Andreadis, A., & Caillet‐Boudin, M. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2005.12.003 · Cited by 62 · see citing works
Self-citationRegulation of alternative splicing of tau exon 10 by 9G8 and Dyrk1A
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Glycation alter the process of Tau phosphorylation to change Tau isoforms aggregation property
Liu, K., Liu, Y., Li, L., Qin, P., Iqbal, J., Deng, Y., & Qing, H. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.12.002 · Cited by 60 · see citing works
- Authors
- Andreadis, A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Andreadis, Athena
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 1739
- Issue
- 2-3
- Pages
- 91-103
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2013013393
- Cited by
- 311
- References
- 111
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 17 · 2023: 13 · 2022: 24 · 2021: 22 · 2020: 25 · 2019: 15 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 6 · 2014: 15 · 2013: 6 · 2012: 15
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institute on Aging
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tau protein, alternative splicing, tau isoforms, splicing regulation, cis-regulatory elements, trans-acting factors, neurofibrillary tangles, neurodegenerative diseases, neuronal cytoskeleton, microtubule binding, neuronal morphology, tau overexpression, dementia
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Brain, Gene Expression Regulation, Humans, Molecular Sequence Data, tau Proteins, Alternative Splicing, Neurodegenerative Diseases, Protein Isoforms, Mice
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