This review concentrates on the molecular pathology of the protein tau, including its expression in various regions of the brain. The role of post-translational modifications in fibrillogenesis is also discussed, particularly hyperphosphorylation and glycation. However, the initiating event that causes aberrant tau processing remains unclear.

OBJECTIVE To investigate intracerebral insulin resistance and its relationship with tau-protein hyperphosphorylation. METHODS A rat model of type 2 diabetes (T2D) was established with streptozotocin (STZ). Diabetic rats received intragastric administration of pioglitazone (PIO group) or normal saline (T2D group) for 4 weeks. As a control, non-diabetic rats received intragastric normal saline ...

A current challenge of cell biology is to investigate molecular interactions in subcellular compartments of living cells to overcome the artificial character of in vitro studies. To dissect the interaction of the neuronal microtubule (MT)-associated protein tau with MTs in axon-like processes, we used a refined fluorescence decay after photoactivation approach and single-molecule tracking. We f...

Alzheimer's disease is the most common form of dementia. Abnormal hyperphosphorylation of Microtubule associated protein tau (MAPT) is one of the hallmarks of Alzheimer's disease and related tau pathies. CDK5 and GSK3B are the two main protein kinases that have an important role in the abnormal hyperphosphorylation of MAPT which leads to Alzheimer's disease. Structural information for both MAPT...

Accumulation of abnormally hyperphosphorylated tau (P-tau) in the form of tangles of paired helical filaments and/or straight filaments is one of the hallmarks of Alzheimer's disease (AD) and other tauopathies. P-tau is also found unpolymerized in AD. Although the cognitive decline is known to correlate with the degree of neurofibrillary pathology, whether the formation of filaments or the prec...

Pathological hyperphosphorylation of the microtubule-associated protein tau is characteristic of Alzheimer’s disease (AD) and the associated tauopathies. The reciprocal relationship between phosphorylation and O-GlcNAc modification of tau and reductions in O-GlcNAc levels on tau in AD brain offers motivation for the generation of potent and selective inhibitors that can effectively enhance O-Gl...

Tau hyperphosphorylation is thought to underlie tauopathy. Working in a Drosophila tauopathy model expressing a human Tau mutant (hTauR406W, or Tau(∗)), we show that zinc contributes to the development of Tau toxicity through two independent actions: by increasing Tau phosphorylation and, more significantly, by directly binding to Tau. Elimination of zinc binding through amino acid substitution...

Hyperphosphorylation of Tau, a protein that stabilizes microtubules, leads to the breakdown of the microtubular structure and ultimately to the formation of neurofibrillar tangles within neurons. Here, we report monitoring of Tau phosphorylations electrochemically, using Tau protein films chemically linked to gold surfaces and 5'-γ-ferrocenyl (Fc) adenosine triphosphate (Fc-ATP) as a co-substra...

Abnormal tau aggregation is a pathological hallmark of many neurodegenerative disorders and it is becoming apparent that soluble tau aggregates play a key role in neurodegeneration and memory impairment. Despite this pathological importance, there is currently no single method that allows monitoring soluble tau species in living cells. In this regard, we developed a cell-based sensor that visua...