Tau AlzheimerAlzheimer' s tau
Alzheimer' s Alzheimer' s disease causes a tau to aggregate into distorted fibrilles that cause confusion in the NEURON. In this case, the function of the cerebral system is impaired and causes the signs of the illness. Due to its pivotal part in the development of Alzheimer's and other neuro-degenerative disorders known as tauopathy (e.g. Pick's disease), Tau has become one of the most active therapy goals in academia and commerce.
However, one of the biggest challenge is the capability to isolation and investigation of the large number of post-translational modification (PTMs) Tau is undergoing before it becomes intoxic. Hilal Lashuel and Mahmood Haj-Yahya have reported in an article in JACS on a new methodology that allows researchers to implement and investigate the impact of PTM in Tau.
It has been journalized in the Journal of the American Chemical Society. It is a technique that consists of constructing a set of peptides from a fragment of polypeptides that are either synthesized by chemical means or express in a cell and then synthesized in a test glass, almost like Legos. The researchers were able to synthesize tau from five segments of tauoprotein ( (441 aminos).
This" semi-synthetic" approach provides great versatility to incorporate one or more altered immune acid at the required locations in each component. It also retains the natural Tau sequences, as well as the parts that have recently been shown to have an important role in disease-related workings. In order to show the versatility of their methodologies, the researchers created variations of dew with different kinds of PTM in different parts of the proteina.
"Our semi-synthetic strategy not only allows the systematical study of site-specific post-translational modification, but for the first study of crosstalk between different modification in the major areas of the molecule that plays a role in the regulation of Tau accumulation and functionality," says Mahmood Haj-Yaha, the Postdoct.
Lashuel's laboratory is now planning to use this method to create a dew libraries that represent the variety of human and pathologic variants of the proteins found in the brains and in biologic liquids. You will then use a series of biologic and chemical tests to find which of these alterations inhibits or aggravates tau accumulation and intoxicity in order to find new therapeutical goals and avenues for the management of Alzheimer's diseas.