Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3β Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy

المؤلفون المشاركون

Nagendra, H. G.
Kumar Dasappa, Jagadeesh

المصدر

International Journal of Alzheimer's Disease

العدد

المجلد 2013، العدد 2013 (31 ديسمبر/كانون الأول 2013)، ص ص. 1-8، 8ص.

الناشر

Hindawi Publishing Corporation

تاريخ النشر

2013-10-10

دولة النشر

مصر

عدد الصفحات

8

التخصصات الرئيسية

الأمراض
الطب البشري

الملخص EN

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta peptides (Aβ) and neurofibrillary tangles (NFTs).

The abnormal phosphorylation of tau leads to the formation of NFTs produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia.

Hence, tau kinases have become potential drug target candidates for small molecule inhibitors.

With an aim to explore the identification of a common inhibitor, this investigation was undertaken towards analyzing all 10 tau kinases which are implicated in phosphorylation of AD.

A set of 7 inhibitors with varied scaffolds were collected from the Protein Data Bank (PDB).

The analysis, involving multiple sequence alignment, 3D structural alignment, catalytic active site overlap, and docking studies, has enabled elucidation of the pharmacophoric patterns for the class of 7 inhibitors.

Our results divulge that tau protein kinases share a specific set of conserved structural elements for the binding of inhibitors and ATP, respectively.

The scaffold of 3-aminopyrrolidine (inhibitor 6) exhibits high preferential affinity with GSK3β.

Surprisingly, the PDB does not contain the structural details of GSK3β with this specific inhibitor.

Thus, our investigations provide vital clues towards design of novel off-target drugs for Alzheimer’s.

نمط استشهاد جمعية علماء النفس الأمريكية (APA)

Kumar Dasappa, Jagadeesh& Nagendra, H. G.. 2013. Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3β Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy. International Journal of Alzheimer's Disease،Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-499817

نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)

Kumar Dasappa, Jagadeesh& Nagendra, H. G.. Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3β Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy. International Journal of Alzheimer's Disease No. 2013 (2013), pp.1-8.
https://search.emarefa.net/detail/BIM-499817

نمط استشهاد الجمعية الطبية الأمريكية (AMA)

Kumar Dasappa, Jagadeesh& Nagendra, H. G.. Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3β Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy. International Journal of Alzheimer's Disease. 2013. Vol. 2013, no. 2013, pp.1-8.
https://search.emarefa.net/detail/BIM-499817

نوع البيانات

مقالات

لغة النص

الإنجليزية

الملاحظات

Includes bibliographical references

رقم السجل

BIM-499817