THERAPEUTIC POTENTIAL OF PROTEIN TYROSINE PHOSPHATASE INHIBITORS- NSC 87877 + VO-OHpic IN PRECLINICAL MODELS OF ALZHEIMER'S DISEASE
Year: 2024
Type: article
Abstract: 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 NSC 87877 + VO-OHpicdemonstrated attenuation of oxidative imbalance, improved mitochondrial activity, and reversed tau pathology. NSC 87877 + VO-OHpic 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.
Author: Sivamallikarjuna Reddy Ambati, M. Mohan Varma, Eswar Kumar Kilari, Ramesh Alluri, Asra Tabassum
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6949382139
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