E3 ubiquitination ligase XIAP lightens diabetes-induced cognitive impairment by inactivating TXNIP-ERS-mediated neuronal injury

Kaohsiung J Med Sci. 2024 Dec 4:e12913. doi: 10.1002/kjm2.12913. Online ahead of print.

Abstract

Diabetes-induced cognitive dysfunction (DCD) is a neurological disorder associated with diabetes, characterized by cognitive impairment driven by neuronal injury from chronic high glucose (HG) exposure. This study aims to elucidate the role and mechanisms of the X-linked inhibitor of apoptosis protein (XIAP)/thioredoxin-interacting protein (TXNIP) in hippocampal neuron cell death and cognitive function within DCD models. A diabetic rat model was established using a high-fat/sucrose diet and streptozotocin injection. Primary hippocampal neurons were stimulated with HG to mimic diabetic conditions. Cognitive and memory functions were assessed using the Morris water maze (MWM) and novel object recognition test (ORT).

Keywords: TXNIP; XIAP; diabetes‐induced cognitive dysfunction; endoplasmic reticulum stress.