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Investigation of lupane triterpene as a novel PTP1B allosteric inhibitor for the improvement of neurite outgrowth and synaptogenesis

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posted on 2024-11-12, 10:06 authored by Tiantian Jin
An impaired synaptogenesis is known to be a common neuropathology in a number of severe mental disorders including schizophrenia, Parkinson disease, bipolar and dementia. Protein tyrosine phosphatase 1B(PTP1B) has been reported to impair neurite outgrowth and synaptic formation via attenuating Brain-derived neurotropic factor (BDNF)-mediated signalling. Leptin signalling also facilitates BDNF and promotes synaptogensis which is inhibited by PTP1B. Therefore PTP1B is a potential drug target to reverse BDNF-mediated neurogensis. In this study, lupane triterpenes, a cluster of natural products, are determined as novel PTP1B allosteric inhibitors which inhibit PTP1B with strong potency and selectivity. Lupane triterpenes inhibit psychotomimetic drug-induced PTP1B and reverse PTP1B-caused BDNF reduction and neurogenesis impairment, indicating that lupane triterpenes are potential drug candidates for PTP1B inhibition and PTP1B-related neurological disorders.

History

Year

2017

Thesis type

  • Doctoral thesis

Faculty/School

School of Medicine

Language

English

Disclaimer

Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.

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