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The role of tau in neurodegeneration

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Gendron, Tania F, Petrucelli, Leonard·2009·Molecular Neurodegeneration
DOI 10.1186/1750-1326-4-13PMC PMC2663562
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Abstract

Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remain unclear, as do the mechanism(s) by which they cause neuronal death. Nonetheless, it is believed that tau-mediated neurodegeneration is likely to result from a combination of toxic gains of function as well as from the loss of normal tau function. To truly appreciate the detrimental consequences of aberrant tau function, a better understanding of all functions carried out by tau, including but not limited to the role of tau in microtubule assembly and stabilization, is required. This review will summarize what is currently known regarding the involvement of tau in the initiation and development of neurodegeneration in tauopathies, and will also highlight some of the remaining questions in need of further investigation.

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  • The increase in hyperphosphorylated tau is likely indicative of neuronal debilitation that has culminated from the accumulation of neurotoxic Aβ.

    “This increase in hyperphosphorylated tau is likely indicative of neuronal debilitation (Gendron and Petrucelli, 2009; Kanno et al., 2014) that has culminated from the accumulation of neurotoxic Aβ.”

    From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Gendron and Petrucelli, 2009

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Authors
Gendron, T. F., & Petrucelli, L.
Affiliations
Mayo Clinic (US)
Corresponding author
Petrucelli, Leonard
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2009
Volume
4
Issue
1
Pages
13
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-4-13
PMC
PMC2663562
OpenAlex
W2050644696
Cited by
478
References
21
Citations by year
2026: 25 · 2025: 35 · 2024: 41 · 2023: 33 · 2022: 29 · 2021: 34 · 2020: 28 · 2019: 22 · 2018: 26 · 2017: 34 · 2016: 23 · 2015: 18 · 2014: 29 · 2013: 20 · 2012: 20
FWCI
17.95
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alzheimer's Association
  • National Institutes of Health (AG17216)
  • National Institute on Aging (P01AG017216)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
tau protein, neurodegeneration, tauopathy, Alzheimer's disease, frontotemporal dementia, neurofibrillary tangles, tau aggregation, neuronal cell death, tau phosphorylation, tau truncation, microtubule stabilization, gain-of-function toxicity

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