Year
2016
Degree Name
Doctor of Philosophy
Department
School of Medicine
Recommended Citation
Jin, Tiantian, Investigation of lupane triterpene as a novel PTP1B allosteric inhibitor for the improvement of neurite outgrowth and synaptogenesis, Doctor of Philosophy thesis, School of Medicine, University of Wollongong, 2016. https://ro.uow.edu.au/theses/4931
Abstract
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 neurotrophic factor (BDNF)-mediated signalling. Leptin signalling also facilitates BDNF and promotes synaptogenesis which is inhibited by PTP1B. Therefore PTP1B is a potential drug target to reverse BDNF-mediated neurogenesis. 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.
FoR codes (2008)
0601 BIOCHEMISTRY AND CELL BIOLOGY, 1109 NEUROSCIENCES, 060105 Cell Neurochemistry, 110903 Central Nervous System
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.