THERAPEUTIC POTENTIAL OF PROTEIN TYROSINE PHOSPHATASE INHIBITORS- SF 1670 + BVT 948 IN PRECLINICAL MODELS OF ALZHEIMER'S DISEASE

Sporadic Alzheimer’s disease (sAD) is the most common type of dementia and progressive neurodegenerative disease. To establish the sAD model, intracerebroventricular (ICV) Streptozocin (STZ) at a dose of 3 mg/kg was administered bilaterally in rats on a stereotaxic apparatus. Three treatment doses of Protein Tyrosine Phosphatase (PTP) inhibitors and Donepezil (2 mg/kg) were given orally to ICV-STZ induced rats for 21 days. Behavioural tests such as Morris water maze (MWM), novel object recognition (NOR) and open field test were performed to evaluate cognitive and locomotor functions. Behavioural results with PTP inhibitor and Donepezil treatment revealed decreased escape latency and increased discrimination index in MWM and NOR respectively. Treatment results with SF 1670 + BVT 948 demonstrated attenuation of oxidative imbalance, improved mitochondrial activity, and reversed tau pathology. SF 1670 + BVT 948 results were compared with standard drug Donepezil. PTP inhibition dose-dependently and significantly improved ICV-STZ-induced cognitive impairment and attenuated the altered anti oxidative related parameters including superoxide dismutase and glutathione. The memory enhancement by PTP inhibition was mediated through oxidative balance, mitochondrial enzyme complex activation, and improved insulin signalling regulation. Further, the increased Aβ protein expression levels in brain tissue were markedly restored with the PTP inhibition treatment. In conclusion, our study demonstrated that PTP inhibition exhibited potential in attenuating STZ-induced sporadic AD features in rats and may be developed as a therapeutic agent in the treatment and management of sporadic AD.