Tyrosine protein kinase ABL1 regulates the mTOR/ULK1 pathway to alleviate postoperative cognitive dysfunction in aged mice.

Feb 3, 2026Histology and histopathology

Protein ABL1 helps reduce memory problems after surgery by controlling cell repair pathways in older mice

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Abstract

Silencing ABL1 improved cognitive deficits in aged mice with postoperative cognitive dysfunction (POCD).

ABL1 may play a role in exacerbating POCD by promoting neuroinflammation and abnormal cell recycling processes in the brain.
Intervention with ABL1 silencing or 3-Methyladenine (3-MA) led to reduced microglial activation and inflammation in the hippocampus.
Knockdown of ABL1 in microglial cells decreased inflammatory responses and protected against neuronal damage.
ABL1 was identified as a direct binding partner of mTOR, suggesting a specific pathway influencing cognitive function.
Inhibition of the ABL1-mTOR signaling pathway could be a potential approach for preventing or treating POCD.

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BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common and serious complication in older adult patients. While the tyrosine kinase ABL1 has been implicated in neurodegenerative diseases, its specific role in POCD remains unexplored. This study aims to investigate whether ABL1 influences POCD in aged mice by regulating microglial autophagy and neuroinflammation via the mTOR/ULK1 pathway.

METHODS: An aged mouse model of POCD was established, and ABL1 silencing and 3-Methyladenine (3-MA) were used to intervene in mice. The Novel Object Recognition Test (NORT) assessment and water maze experiment were conducted. qRT-PCR quantified the mRNA levels of inflammatory cytokines, hippocampal damage was assessed by immunofluorescence, and western blot analyzed the protein expression of autophagy-related genes and the mTOR/ULK1 pathway. Co-Immunoprecipitation (CO-IP) was used to detect the binding of ABL1 to mTOR.experiments used microglial cells, wheresilencing and rapamycin (Rapa) were used to construct a cellular model and conduct relevant cell experiments. In vitro ABL1

RESULTS: silencing or 3-MA rescued cognitive deficits in aged POCD mice, concurrently mitigating neuroinflammation, microglial activation, and aberrant autophagy in the hippocampus. We established ABL1 as a direct binding partner of mTOR. Silencingactivated thepathway, leading toinhibition and suppression of autophagic activity. Consistent with theseresults,knockdown in microglia attenuated pro-inflammatory responses, inhibited autophagy, and conferred protection against neuronal damage. ABL1ABL1mTOR ULK1in vivo ABL1

CONCLUSIONS: exacerbates POCD in aged mice by promoting microglial autophagy and neuroinflammation through thesignaling pathway. Targeted inhibition ofmay represent a novel therapeutic strategy for preventing or treating POCD. ABL1mTOR/ULK1ABL1

Tyrosine protein kinase ABL1 regulates the mTOR/ULK1 pathway to alleviate postoperative cognitive dysfunction in aged mice.

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