Exosomes, nano-sized lipid bilayer vesicles, have garnered significant attention as mediators of cell communication, particularly within the central nervous system (CNS). Their unique properties, including high stability, low immunogenicity, and the ability to traverse the blood-brain barrier (BBB), position them as promising tools for understanding and addressing CNS diseases. This comprehensive review delves into the biogenesis, properties, composition, functions, and isolation of exosomes, with a particular focus on their roles in cerebrovascular diseases, neurodegenerative disorders, and CNS tumors. Exosomes are involved in key pathophysiological processes in the CNS, including angiogenesis, inflammation, apoptosis, and cellular microenvironment modification. They demonstrate promise in mitigating ischemic injury, regulating inflammatory responses, and providing neuroprotection across various CNS conditions. Furthermore, exosomes carry distinct biomolecules, offering a novel method for the early diagnosis and monitoring of CNS diseases. Despite their potential, challenges such as complex extraction processes, the heterogeneity of exosomal contents, and targeted delivery limitations hinder their clinical application. Nevertheless, exosomes hold significant promise for advancing our understanding of CNS diseases and developing novel therapeutic strategies. This manuscript significantly contributes to the field by highlighting exosomes' potential in advancing our understanding of CNS diseases, underscoring their unique value in developing novel therapeutic strategies and mediating cellular communication.
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http://dx.doi.org/10.3390/biom14121519 | DOI Listing |
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
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View Article and Find Full Text PDFBackground: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFBackground: The hyperphosphorylation, mislocalization, and aggregation of the microtubule associated protein Tau (MAPT) is a driving force in tauopathies, a group of progressive, neurodegenerative disorders. These pathogenic intracellular aggregates, known as neurofibrillary tangles (NFTs), are a hallmark in several diseases such as frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's Disease. While anti-Tau immunotherapies emphasize the clearance of extracellular Tau aggregates, they do not address the intracellular accumulation of NFTs.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
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