Long Non-Coding RNA PART1 in Alzheimer's Disease: Clinical Value and Improvement of Neurotoxicity and Apoptosis via miR-770-5p.

Dysregulation of long non-coding RNA (lncRNA) PART1 is associated with neurodegenerative diseases, but its role in Alzheimer's disease (AD) remains unclear. This study investigated the clinical significance of PART1 in AD and its potential neuroprotective mechanisms, aiming to offer new insights for risk prediction and mechanism research. Serum PART1 levels were detected in 258 participants using real-time quantitative PCR (RT-qPCR), including 70 controls, 88 patients with amnestic mild cognitive impairment (aMCI), and 100 patients with AD. In vitro AD models were established using SH-SY5Y cells treated with amyloid-β peptide 25-35 (Aβ25-35). Functional assays were performed, including flow cytometry and Cell Counting Kit-8 (CCK-8) assay, along with the detection of oxidative stress levels. Mechanism studies included bioinformatic predictions and luciferase reporter assays. Serum PART1 was significantly downregulated in patients with aMCI and AD, and positively correlated with Mini-Mental State Examination scores. Low PART1 expression was a risk factor for AD and demonstrated good diagnostic value (AUC = 0.843). Aβ downregulated PART1 in SH-SY5Y cells, while PART1 overexpression attenuated Aβ-induced cytotoxicity, apoptosis, and oxidative stress. PART1 directly targeted and negatively regulated miR-770-5p, which was upregulated in AD. The neuroprotective effects of PART1 were reversed by miR-770-5p mimic. Furthermore, bioinformatic analysis and validation experiments identified GRIA2 as a downstream target of miR-770-5p. In summary, serum PART1 is a promising biomarker for AD. PART1 exerts neuroprotective effects against Aβ-induced damage by downregulating the miR-770-5p/GRIA2 axis, suggesting that PART1 is a potential target for intervention strategies in AD.