In Alzheimer's disease (AD), the impaired clearance of β-amyloid peptide (Aβ) due to disrupted tight junction and transporter proteins is the prominent cause of disease progression. Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss. However, the role of SST in preservation of blood-brain barrier (BBB) integrity and functionality in Aβ-induced toxicity is not known. In the present study using human CMEC/D3 cells, we demonstrate that SST prevents Aβ-induced BBB permeability by regulating LRP1 and RAGE expression and improving the disrupted tight junction proteins. Furthermore, SST abrogates Aβ-induced JNK phosphorylation and expression of MMP2. Taken together, results presented here suggest that SST might serve as a therapeutic intervention in AD via targeting multiple pathways responsible for neurotoxicity, impaired BBB function, and disease progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12035-018-1045-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Overexpression of FTO alleviates traumatic brain injury induced posttraumatic epilepsy by upregulating NR4A2 expression via m6A demethylation.
Funct Integr Genomics
January 2025
Department of Radiology, The Second Xiangya Hospital of Central South University, No. 139, Renmin Middle Road, Furong District, Changsha City, Hunan Province, 410011, China.
Post-traumatic epilepsy (PTE) is a debilitating chronic outcome of traumatic brain injury (TBI). Although FTO has been reported as a possible intervention target of TBI, its precise roles in the PTE remain incompletely understood. Here we used mild or serious mice TBI model to probe the role and molecular mechanism of FTO in PTE.
View Article and Find Full Text PDFRelaxometry and contrast-free cerebral microvascular quantification using balanced steady-state free precession MR fingerprinting.
Magn Reson Med
January 2025
Université Grenoble Alpes, INSERM, U1216, Grenoble Institute Neurosciences, GIN, Grenoble, France.
Purpose: This study proposes a novel, contrast-free Magnetic Resonance Fingerprinting (MRF) method using balanced Steady-State Free Precession (bSSFP) sequences for the quantification of cerebral blood volume (CBV), vessel radius (R), and relaxometry parameters (T , T , T *) in the brain.
Methods: The technique leverages the sensitivity of bSSFP sequences to intra-voxel frequency distributions in both transient and steady-state regimes. A dictionary-matching process is employed, using simulations of realistic mouse microvascular networks to generate the MRF dictionary.
PSMC2 promotes resistance against temozolomide in glioblastoma via suppressing JNK-mediated autophagic cell death.
Biochem Pharmacol
January 2025
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India. Electronic address:
Temozolomide is universally used to treat glioblastoma due to its unique ability to cross the blood-brain barrier and inhibit tumor growth through DNA alkylation. However, over time, the inevitable emergence of resistance to temozolomide impedes successful treatment of this cancer. As a result, there is an urgent need to identify new therapeutic targets to improve treatment outcomes for this malignancy.
View Article and Find Full Text PDFExercise preconditioning increases circulating exosome miR-124 expression and alleviates apoptosis in rats with cerebral ischemia-reperfusion injury.
Brain Res
January 2025
The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 15000, China. Electronic address:
Objectives: Exercise as a non-pharmacological intervention can exert beneficial effects directly through exosomes crossing the blood-brain barrier and reduce apoptosis after cerebral ischaemia/reperfusion injury (CI/RI). miRNA-124 (miR-124) is present in exosomes and plays an important role in regulating cerebral neurological activity; however, the mechanism of the relationship between exercise and the activity of exosomes and apoptosis after CI/RI remains unclear. Therefore, the present study investigated the effects of exercise preconditioning on cerebral ischemia/reperfusion injury from the perspective of exosomal miR-124 and apoptosis.
View Article and Find Full Text PDFQuercetin-functionalized nanomaterials: Innovative therapeutic avenues for Alzheimer's disease management.
Ageing Res Rev
January 2025
Department of Chemical Technology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address:
Alzheimer's Disease (AD) is a major global health challenge, largely due to its complex pathology and the limited effectiveness of existing treatments. Quercetin, a bioactive compound belonging to the flavonoid class, its promising antioxidant, anti-inflammatory, and neuroprotective effects in addressing AD. However, its therapeutic potential is hindered by challenges such as low bioavailability, instability, and restricted permeability across the blood-brain barrier (BBB).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!