miércoles, 28 de febrero de 2018

InSysBio evaluates tau protein phosphorylation related targets for treatment of AD

InSysBio evaluates tau protein phosphorylation related targets for treatment of AD

News-Medical

InSysBio evaluates tau protein phosphorylation related targets for treatment of AD

InSysBio continues to investigate the mechanisms underlying Alzheimer's disease (AD) using the quantitative systems pharmacology (QSP) modeling approach. The part of QSP model describing tau protein was published in the PLOS ONE journal. This is one of more than dozen InSysBio publications in AD area during last seven years.
There is still no clear understanding what is the driving force of AD progression. The main hypotheses of the pathology are based on amyloid beta plaques or tau protein aggregation.
Tau protein (or MAPT, microtubule-associated protein tau) stabilizes the cytoskeleton in normal cells, but it doesn't function properly in neurons of AD patients, it undergoes hyperphosphorylation and aggregates into neurofibrillary tangles within neurons. Normally, only some of the numerous phosphorylation sites of tau are phosphorylated. Therefore drugs for the tauopathies treatment could target pathological tau phosphorylation.
Different phosphorylation states contribute unequally in the pathology. So understanding the relative contribution of each kinase and phosphatase to phosphorylation of distinct sites is important for searching the principal drug targets. This was the goal of the work.
If a protein has n phosphorylation sites, then there are 2n possible phosphorylation states. Furthermore, the sequence of protein phosphorylation and dephosphorylation processes is regulated in a complicated way. The model developers assumed that phosphorylation of distinct sites is partially independent. It allowed to overcome the combinatorial explosion problem.
Four kinases (GSK3β, PKA, CDK5 and p38γ) and one phosphatase (PP2A) were selected from the plurality of tau (de)phosphorylating enzymes. Ten phosphorylation sites which are of specific interest for the clinical research were selected from a few dozens of potentially phosphorylable sites of tau protein. This selection was based on the published experimental data. The modelers also have incorporated so-called pseudoresidue which described phosphorylation sites aside from the ten described above. This is the first effort of estimation of tau protein state sensitivity to key enzymes using real kinetic data.
"We've taken the first step in understanding of (de)phosphorylation patterns of each tau protein residue by different enzymes. Our model may suggest the role of each tau kinase or phosphatase plays in AD pathogenesis as well as the most potent targets for its treatment," commented Alexander Stepanov, the leading contributor of the article.
"The published model is another brick in the integrated QSP model which is now developed in InSysBio that may help to find the treatment of AD," said Tatiana Karelina, PhD, Head of the Neurodegenerative Diseases modeling group at InSysBio.

3 comentarios:

  1. I was diagnose with hpv virus for 5years i broke up with my boyfriend because i contracted the virus from him, luckily i found a herbalist name Dr. onokun everyone testify good of his natural treatment i picked up his address and contacted him. he truly treated me with natural herbs in a week and i got cured. i share this post because ever since i got this treatment I'm perfectly ok with my health. i contacted him through this email.. dronokunherbalcure@gmail.com

    ResponderEliminar
  2. 5 years ago I had warts, I was treated with some liquid applied to the warts they continued to grow and spread... The next 2 doctors did laser surgery to remove them. 1 year after the surgery, they grew back close to where the 1st ones were' so I was finally told it was hpv. I have had it for very long time, I contract it from my cheated boyfriend and I found out he was also infected and I end up the relationship between us. the warts was so embarrasses because it started spreading all over I have be dealing with this things for very long time the last treatment I take was About 2 years ago I applied natural treatment from Dr onokun herbal cure, a week after applying the treatment all the warts was gone. it's now 2 years and some months I don't have single wart or any symptoms of hpv. wow"" it's great, Dr onokun has finally cured me. Anyone living with hpv contact Dr onokun for natural treatment.
    His email address: dronokunherbalcure@gm‎ail.com

    ResponderEliminar
  3. Dearest Esteems,

    We are Offering best Global Financial Service rendered to the general public with maximum satisfaction,maximum risk free. Do not miss this opportunity. Join the most trusted financial institution and secure a legitimate financial empowerment to add meaning to your life/business.

    Contact Dr. James Eric Firm via
    Email: fastloanoffer34@gmail.com
    https://urgentloanoffer22.blogspot.com/
    Whatsapp +918929509036
    Best Regards,
    Dr. James Eric.
    Executive Investment
    Consultant./Mediator/Facilitator

    ResponderEliminar