ArticleCNS neuroscience & therapeutics2023
Inhibition of mammalian target of rapamycin complex 1 in the brain microvascular endothelium ameliorates diabetic Aβ brain deposition and cognitive impairment via the sterol-regulatory element-binding protein 1/lipoprotein receptor-associated protein 1 signaling pathway.
Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 10 citations in OpenAlex.
- Upregulation of PPTC7 in brain microvascular endothelial cell aggravates diabetic cognitive dysfunction by impairing PHB2 mediated mitochondrial function.Redox biology · 2026Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Mechanisms of IGF1R signaling in type 2 diabetes-related neurodegeneration and therapeutic implications of exercise.European journal of medical research · 2025Article
- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Blood-brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease.Translational neurodegeneration · 2025Review
- Pharmacological mTOR inhibitors in ameliorating Alzheimer's disease: current review and perspectives.Frontiers in pharmacology · 2024Review
- Inhibition of mammalian target of rapamycin complex 1 in the brain microvascular endothelium ameliorates diabetic Aβ brain deposition and cognitive impairment via the sterol-regulatory element-binding protein 1/lipoprotein receptor-associated protein 1 signaling pathway.CNS neuroscience & therapeutics · 2023Article
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8 authors at 3 institutions in 1 country.
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Abstract
aimsMammalian target of rapamycin complex 1 (mTORC1) is highly activated in diabetes, and the decrease of low-density lipoprotein receptor-associated protein 1 (LRP1) in brain microvascular endothelial cells (BMECs) is a key factor leading to amyloid-β (Aβ) deposition in the brain and diabetic cognitive impairment, but the relationship between them is still unknown.
methodsIn vitro, BMECs were cultured with high glucose, and the activation of mTORC1 and sterol-regulatory element-binding protein 1 (SREBP1) was observed. mTORC1 was inhibited by rapamycin and small interfering RNA (siRNA) in BMECs. Betulin and siRNA inhibited SREBP1, observed the mechanism of mTORC1-mediated effects on Aβ efflux in BMECs through LRP1 under high-glucose conditions. Constructed cerebrovascular endothelial cell-specific Raptor-knockout (Raptor
resultsmTORC1 activation was observed in HBMECs cultured in high glucose, and this change was confirmed in diabetic mice. Inhibiting mTORC1 corrected the reduction in Aβ efflux under high-glucose stimulation. In addition, high glucose activated the expression of SREBP1, and inhibiting of mTORC1 reduced the activation and expression of SREBP1. After inhibiting the activity of SREBP1, the presentation of LRP1 was improved, and the decrease of Aβ efflux mediated by high glucose was corrected. Raptor
conclusionInhibiting mTORC1 in the brain microvascular endothelium ameliorates diabetic Aβ brain deposition and cognitive impairment via the SREBP1/LRP1 signaling pathway, suggesting that mTORC1 may be a potential target for the treatment of diabetic cognitive impairment.
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