Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Mar:178:72-79.
doi: 10.1016/j.mad.2019.01.007. Epub 2019 Jan 19.

Tauopathy: A common mechanism for neurodegeneration and brain aging

Pampa Saha  1 , Nilkantha Sen  2
Affiliations
Review

Tauopathy: A common mechanism for neurodegeneration and brain aging

Pampa Saha et al. Mech Ageing Dev. 2019 Mar.

Abstract

Tau, a microtubule-associated protein promotes assembly and stability of microtubules which is related to axoplasmic flow and critical neuronal activities upon physiological conditions. Under neurodegenerative condition such as in Alzheimer's Disease (AD), tau-microtubule binding dynamics and equilibrium are severely affected due to its aberrant post-translational modifications including acetylation and hyperphosphorylation. This event results in its conformational changes to form neurofibrillary tangles (NFT) after aggregation in the cytosol. The formation of NFT is more strongly correlated with cognitive decline than the distribution of senile plaque, which is formed by polymorphous beta-amyloid (Aβ) protein deposits, another pathological hallmark of AD. In neurodegenerative conditions, other than AD, the disease manifestation is correlated with mutations of the MAPT gene. In Primary age-related tauopathy (PART), which is commonly observed in the brains of aged individuals, tau deposition is directly correlated with cognitive deficits even in the absence of Aβ deposition. Thus, tauopathy has been considered as an essential hallmark in neurodegeneration and normal brain aging. In this review, we highlighted the recent progress about the tauopathies in the light of its posttranslational modifications and its implication in AD and the aged brain.

Keywords: Aging; Alzheimer’s disease; Amyloid beta; Cognitive dysfunction; Neurodegeneration; Tau acetylation; Tau hyperphosphorylation; Tauopathy.

PubMed Disclaimer

Figures

Figure 1:
Figure 1:
Upon induction of amyloid beta, Nitrosylated GAPDH activates an acetyltransferase p300 via direct interaction. On the other hand, it inactivates a deacetylase, SIRT1 by nitrosylates SIRT1 through transnitrosylation reaction. As a result, the level of Tau acetylation remains elevated and accumulation of acetylated tau leads to tau phosphorylation and NFT in AD.
See this image and copyright information in PMC

References

    1. Abou-Sleiman PM, Muqit MM and Wood NW (2006). “Expanding insights of mitochondrial dysfunction in Parkinson’s disease.” Nat Rev Neurosci 7(3): 207–219. - PubMed
    1. Alonso AC, Grundke-Iqbal I and Iqbal K (1996). “Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules.” Nat Med 2(7): 783–787. - PubMed
    1. Alonso AC, Zaidi T, Grundke-Iqbal I and Iqbal K (1994). “Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease.” Proc Natl Acad Sci U S A 91(12): 5562–5566. - PMC - PubMed
    1. Alonso AD, Grundke-Iqbal I, Barra HS and Iqbal K (1997). “Abnormal phosphorylation of tau and the mechanism of Alzheimer neurofibrillary degeneration: sequestration of microtubule-associated proteins 1 and 2 and the disassembly of microtubules by the abnormal tau.” Proc Natl Acad Sci U S A 94(1): 298–303. - PMC - PubMed
    1. Alonso AD, Zaidi T, Novak M, Barra HS, Grundke-Iqbal I and Iqbal K (2001). “Interaction of tau isoforms with Alzheimer’s disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein.” J Biol Chem 276(41): 37967–37973. - PubMed

Publication types