The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is one of the characteristic hallmarks of Alzheimer's disease (AD). Aβ-peptide brain homeostasis is governed by its production and various clearance mechanisms. The blood-brain barrier provides a large surface area for influx and efflux mechanisms into and out of the brain. Different transporters and receptors have been implicated to play crucial roles in Aβ clearance from brain. Besides Aβ transport, the blood-brain barrier tightly regulates the brain's microenvironment; however, vascular alterations have been shown in patients with AD. Here, we summarize how the blood-brain barrier changes during aging and in disease and focus on recent findings of how the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) play a role in Aβ clearance from brain.
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http://dx.doi.org/10.1007/164_2020_418 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.
CRISPR/Cas9 (CRISPR, clustered regularly interspaced short palindromic repeats) gene editing technology represents great promise for treating glioblastoma (GBM) due to its potential to permanently eliminate tumor pathogenic genes. Unfortunately, delivering CRISPR to the GBM in a safe and effective manner is challenging. Herein, a glycosylated and cascade-responsive nanoparticle (GCNP) that can effectively cross the blood-brain barrier (BBB) and activate CRISPR/Cas9-based gene editing only in the GBM is designed.
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
Modern radiotherapy frequently employs radiosensitizers for radiation dose deposition and triggers an immunomodulatory effect to enhance tumor destruction. However, developing glioma-targeted sensitizers remains challenging due to the blood-brain barrier (BBB) and multicomponent instability. This study aims to green-synthesize transferrin-bismuth nanoparticles (TBNPs) as biosafe radiosensitizers to enhance X-ray absorption by tumors and stimulate the immune response for glioma therapy.
View Article and Find Full Text PDFSmall
January 2025
Cancer Hospital of Dalian University of Technology, Dalian University of Technology, Shenyang, 110042, China.
Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to the existing immunotherapies due to the significant immunosuppression within tumor microenvironment (TME), predominantly manipulated by M2-phenotypic tumor-associated macrophages (M2-TAMs). Here in this work, an M2-TAMs targeted nano-reprogrammers, MG5-S-IMDQ, is established by decorating the mannose molecule as the targeting moiety as well as the toll-like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on the dendrimeric nanoscaffold. MG5-S-IMDQ demonstrated an excellent capacity of penetrating the blood-brain barrier (BBB) as well as selectively targeting M2-TAMs in the GBM microenvironment, leading to a phenotype transformation and function restoration of TAMs shown as heightened phagocytic activity toward tumor cells, enhanced cytotoxic effects, and improved tumor antigen cross-presentation capability.
View Article and Find Full Text PDFChemistryOpen
January 2025
Department of Chemistry, Faculty of Sciences, University of Guilan, Rasht, 4193833697, Iran.
The inhibition of acetylcholinesterase (AChE), an enzyme responsible for the inactivation and decrease in acetylcholine in the cholinergic pathway, has been considered an attractive target for small-molecule drug discovery in Alzheimer's disease (AD) therapy. In the present study, a series of TZD derivatives were designed, synthesized, and studied for drug likeness, blood-brain barrier (BBB) permeability, and adsorption, distribution, metabolism, excretion, and toxicity (ADMET). Additionally, docking studies of the designed compounds were performed on AChE.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Diagnostic Imaging, Oncologic Radiotherapy and Hematology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00100 Rome, Italy.
The growing interest in minimal and non-invasive therapies, especially in the field of cancer treatment, highlights a significant shift toward safer and more effective options. Ablative therapies are well-established tools in cancer treatment, with known effects including locoregional control, while their role as modulators of the systemic immune response against cancer is emerging. The HIFU developed with magnetic resonance imaging (MRI) guidance enables treatment precision, improves real-time procedural control, and ensures accurate outcome assessment.
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