Cited by 311Alzheimer's disease research and treatmentsRNA Research and SplicingAmyotrophic Lateral Sclerosis Research

Tau gene alternative splicing: expression patterns, regulation and modulation of function in normal brain and neurodegenerative diseases

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Andreadis, Athena·2005·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

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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Crossref · 10.1016/j.bbadis.2004.08.010

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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).”

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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
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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