Work

Pharmacological PTP1B inhibition rescues motor learning, neuroinflammation, and hyperglycaemia in a mouse model of Alzheimer's disease

Year: 2024

Type: article

Abstract: BACKGROUND: ) controls. METHODS: mice received PTP1B inhibitor treatment (1 mg/kg intraperitoneal injection; 5 weeks). Activity and spatial habituation (Phenotyper), motor learning (RotaRod), glucose tolerance, and brain and liver molecular analyses were analysed following treatment. RESULTS: Inhibition of PTP1B improved motor learning alongside glucose tolerance in PLB4 mice, without affecting body weight/adiposity. MSI-1436 treatment led to lower protein levels of amyloid precursor protein (APP), reduced astrogliosis and restoration of the endoplasmic chaperone immunoglobulin heavy chain binding protein (BIP) in the brain, alongside decreased insulin receptor substrate-1 (IRS1) and dipeptidyl peptidase-4 (DPP4) proteins in the liver. CONCLUSION: We provide evidence that neuronal BACE1 contributes to neuroinflammation and hyperglycaemia in PLB4 mice, and this can be partially rescued by PTP1B inhibition. Targeting PTP1B may therefore offer an attractive therapeutic approach to ameliorate co-morbidity associated pathologies in AD and T2DM.

Source: Experimental Neurology

DOI: 10.1016/j.expneurol.2024.115115

Authors: Zara Franklin, Claire Hull, Mirela Delibegovic, Bettina Platt

Institution: University of Aberdeen

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,810