Tau in physiology and pathology

  title={Tau in physiology and pathology},
  author={Yi-peng Wang and Eckhard Mandelkow},
  journal={Nature Reviews Neuroscience},
Tau is a microtubule-associated protein that has a role in stabilizing neuronal microtubules and thus in promoting axonal outgrowth. Structurally, tau is a natively unfolded protein, is highly soluble and shows little tendency for aggregation. However, tau aggregation is characteristic of several neurodegenerative diseases known as tauopathies. The mechanisms underlying tau pathology and tau-mediated neurodegeneration are debated, but considerable progress has been made in the field of tau… 
Tau Toxicity in Neurodegeneration.
The normal physiological function and dysfunction of tau proteins are described and the enzymes and proteins involved in tau phosphorylation and dephosphorylation are discussed, the role of t Tau in cell dysfunction, and the relationships between tau and several neurodegenerative diseases are discussed.
Roles of tau protein in health and disease
It is important to fully understand the range of neuronal functions attributed to tau, since this will provide vital information on its involvement in the development and pathogenesis of disease, and enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies.
It’s all about tau
Dendritic Tau in Alzheimer’s Disease
Altered Proteostasis in Neurodegenerative Tauopathies.
The response of the Ubiquitin-Proteasome system, autophagy and the Endoplasmic Reticulum-Unfolded Protein response in Tauopathy models and patients is discussed, revealing interactions of components of these systems with Tau, but also of the effects of pathological Tau on these systems which eventually lead to Tau aggregation and accumulation.
The Neurotoxic Role of Extracellular Tau Protein
The neurotoxic role of extracellular tau as well its involvement in the spreading of tau pathologies are discussed.
Tau in Health and Neurodegenerative Diseases
The role of t Tau protein in physiological conditions and the pathological changes of tau related to neurodegenerative diseases are reviewed and the applications of tAU as a therapeutic target are discussed.
The Structure Biology of Tau and Clue for Aggregation Inhibitor Design
In this review, recent progress on the structural investigation of tau is summarized and a new aggregation inhibitor design is discussed based on which the aggregate structure of t Tau is formed by closed packing of β-stands.
Role of the Lipid Membrane and Membrane Proteins in Tau Pathology
The recent literature on the mechanisms of the tau-membrane interaction is reviewed and the roles of lipids and proteins at the membrane in the t Tau-memBRane interaction as well as tau aggregation are highlighted.
The Metamorphic Nature of the Tau Protein: Dynamic Flexibility Comes at a Cost
This review will focus on how the distinct structure of tau governs its function, accumulation, and toxicity as well as how other cellular factors such as molecular chaperones control these processes.


Microtubule-associated protein tau is essential for long-term depression in the hippocampus
It is found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau, which demonstrates that tau has a critical physiological function in LTD.
Biochemistry and cell biology of tau protein in neurofibrillary degeneration.
The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming β structures.
Misregulation of tau alternative splicing in neurodegeneration and dementia.
  • A. Andreadis
  • Biology
    Progress in molecular and subcellular biology
  • 2006
This review briefly presents the cumulative knowledge of tau splicing regulation in connection with the alterations in t Tau splicing seen in neurodegeneration.
The microtubule-associated tau protein has intrinsic acetyltransferase activity
It is reported that mammalian tau proteins possess intrinsic enzymatic activity capable of catalyzing self-acetylation, suggesting a mechanism similar to that employed by MYST-family acetyltransferases.
Degradation of tau protein by autophagy and proteasomal pathways.
This paper focuses on the regulation of the degradation of tau by the UPS and ALS and its relation to tau aggregation, and expects that stimulation of these two protein-degradation systems might be a potential therapeutic strategy for AD and other tauopathies.
Oligomer Formation of Tau Protein Hyperphosphorylated in Cells*
Hyperphosphorylation does not drive Tau fibrillization but contributes to synaptotoxicity, and the role of phosphorylation and the distinction between physiological and pathological phosphorylated needs to be further refined.
Tau stabilizes microtubules by binding at the interface between tubulin heterodimers
Detailed insight is provided into the Tau–microtubule association by using NMR spectroscopy and mass spectrometry to show that Tau binds to microtubules by using small groups of evolutionary conserved residues, which are important for pathological aggregation of Tau.
Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity.
These findings suggest that the nonfibrillized P-tau is most likely the responsible entity for the disruption of microtubules in neurons in AD and the efforts in finding a therapeutic intervention for tau-induced neurodegeneration need to be directed either to prevent the abnormal hyperphosphorylation of this protein or to neutralize its binding to normal MAPs.