The microtubule-associated protein tau is essential for microtubule stabilization in neuronal axons. Hyperphosphorylation and intracellular fibrillar formation of tau protein is a pathology found in Alzheimer's disease (AD) brains, and in a variety of neurodegenerative disorders referred to as 'taupathies'. In the present study, we investigated how brain-derived neurotrophic factor (BDNF), an e...

Tau is a microtubule-associated protein which regulates the assembly and stability of microtubules in the axons of neurons. Tau is also a major component of neurofibrillary tangles (NFTs), a pathological hallmark in Alzheimer's disease (AD). A characteristic of AD tau is hyperphosphorylation with more than 40 phosphorylation sites. Aggregates of hyperphosphorylated tau are also found in other n...

Hyperphosphorylation of the microtubule associated protein tau is detected in the brains of individuals with a range of neurodegenerative diseases including Alzheimer's disease (AD). An imbalance in phosphorylation and/or dephosphorylation of tau at disease-related sites has been suggested to initiate the abnormal metabolism and toxicity of tau in disease pathogenesis. However, the mechanisms u...

Tau protein plays an important role in neuronal physiology and Alzheimer's neurodegeneration. Its abilities to aggregate abnormally, to bind to microtubules (MTs), and to promote MT assembly are all influenced by phosphorylation. Phosphorylation of serine residues in the KXGS motifs of Tau's repeat domain, crucial for MT interactions and aggregation, is facilitated most efficiently by microtubu...

Almost a 20% of the residues of tau protein are phosphorylatable amino acids: serine, threonine, and tyrosine. In this paper we comment on the consequences for tau of being a phosphoprotein. We will focus on serine/threonine phosphorylation. It will be discussed that, depending on the modified residue in tau molecule, phosphorylation could be protective, in processes like hibernation, or toxic ...

Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathol...

One of the important neuropathological features of Alzheimer’s disease (AD) is the tau pathology seen as accumulation and hyperphosphorylation of this protein. Evidences showed that tau could be phosphorylated mostly at serine/threonine (S/T) residues by many kinases, including protein kinase B, glycogen synthase kinase (GSK)-3β, extracellular signal-regulated kinase (ERK1/2), ERK1/2 kinase (ME...

NMR spectroscopy was used to explore the different aspects of the normal and pathological functions of tau, but proved challenging because the protein contains 441 amino acids and has poor signal dispersion. We have set out to dissect the phosphorylation patterns of tau in order to understand better its role in the aggregation process and microtubule-binding regulation. Our current knowledge on...

p44 is a short isoform of p53 with 'longevity-assurance' activity. Overexpression of p44 in the mouse (p44(+/+) transgenic mice) causes a progeroid phenotype that mimics an accelerated form of aging. The phenotype includes abnormal phosphorylation of the microtubule-binding protein tau, synaptic deficits, and cognitive decline. Genetic engineering demonstrated that the phosphorylation status of...

The axonal microtubule stabilizing protein tau is hyperphosphorylated in several neurodegenerative conditions, including Alzheimer's disease, yet the genes that regulate tau phosphorylation are largely unknown. Disabled-1 (Dab1) is a cytoplasmic adapter protein that interacts with apolipoprotein E (ApoE) receptors and controls neuronal positioning during embryonic brain development. We have inv...