The up-regulation of PTBP1 expression level in patients with Insomnia by senile dementia and promote cuproptosis of nerve cell by SLC31A1

Abstract

Alzheimer's disease (AD), often referred to as the modern-day scourge, stands as a significant health challenge characterized by high rates of disability and mortality, particularly among the geriatric population. Thus, the present study investigated the precise details of PTBP1 involvement in cuproptosis of nerve cell of patients with Insomnia by senile dementia (ISD). Patients with ISD, early mild cognitive impairment (EMCI) and Normal healthy volunteers were obtained.

In the context of ISD, the elevated PTBP1 mRNA expressions were observed in patient samples, correlating positively with diminished cognitive function as measured by the Mini-Mental State Examination (MMSE) and increased geriatric depression scale scores. The pivotal role of PTBP1 was further underscored by its inhibitory effects in a mice model, which prevented the development of senile dementia, and its influence on neuronal cell proliferation and ROS-induced oxidative stress in vitro. Additionally, PTBP1's regulatory capacity on the cuproptosis of nerve cells and its modulation of SLC31A1 expression, through effects on ubiquitination, were revealed. The stability of PTBP1, critical for its function, was enhanced by the m6A modification mediated by METTL3, highlighting a complex regulatory network in the pathogenesis of ISD.

These data confirmed that PTBP1 plays a pivotal role in promoting the oxidative response and cuproptosis in Alzheimer's disease models via the SLC31A1 pathway. The findings suggest that PTBP1 could serve as a potential biomarker for the diagnosis and prognostic evaluation of ISD and AD, paving the way for the development of novel therapeutic strategies targeting this protein.