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Extracellular Vesicle-Based Therapeutics in Neurological Disorders.

ABSTRACT: Neurological diseases remain some of the major causes of death and disability in the world. Few types of drugs and insufficient delivery across the blood-brain barrier limit the treatment of neurological disorders. The past two decades have seen the rapid development of extracellular vesicle-based therapeutics in many fields. As the physiological and pathophysiological roles of extracellular vesicles are recognized in neurological diseases, they have become promising therapeutics and targets for therapeutic interventions. Moreover, advanced nanomedicine technologies have explored the potential of extracellular vesicles as drug delivery systems in neurological diseases. In this review, we discussed the preclinical strategies for extracellular vesicle-based therapeutics in neurological disorders and the struggles involved in their clinical application.

SUBMITTER: Yuan Y

PROVIDER: S-EPMC9783774 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Extracellular Vesicle-Based Therapeutics in Neurological Disorders.

Yuan Yiwen Y Sun Jian J You Tongyao T Shen Weiwei W Xu Wenqing W Dong Qiang Q Cui Mei M

Pharmaceutics 20221130 12

Neurological diseases remain some of the major causes of death and disability in the world. Few types of drugs and insufficient delivery across the blood-brain barrier limit the treatment of neurological disorders. The past two decades have seen the rapid development of extracellular vesicle-based therapeutics in many fields. As the physiological and pathophysiological roles of extracellular vesicles are recognized in neurological diseases, they have become promising therapeutics and targets for ...[more]

PMID: 36559145

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Project description:The complement system consists of a network of plasma and membrane proteins that modulate tissue homeostasis and contribute to immune surveillance by interacting with the innate and adaptive immune systems. Dysregulation, impairment or inadvertent activation of complement components contribute to the pathogenesis of some autoimmune neurological disorders and could even contribute to neurodegenerative diseases. In this Review, we summarize current knowledge about the main functions of the complement pathways and the involvement of complement in neurological disorders. We describe the complex network of complement proteins that target muscle, the neuromuscular junction, peripheral nerves, the spinal cord or the brain and discuss the autoimmune mechanisms of complement-mediated myopathies, myasthenia, peripheral neuropathies, neuromyelitis and other CNS disorders. We also consider the emerging role of complement in some neurodegenerative diseases, such as Alzheimer disease, amyotrophic lateral sclerosis and even schizophrenia. Finally, we provide an overview of the latest complement-targeted immunotherapies including monoclonal antibodies, fusion proteins and peptidomimetics that have been approved, that are undergoing phase I–III clinical trials or that show promise for the treatment of neurological conditions that respond poorly to existing immunotherapies. In this Review, Dalakas et al. discuss the complement system, the role it plays in autoimmune neurological disease and neurodegenerative disease, and provide an overview of the latest therapeutics that target complement and that can be used for or have potential in neurological disorders. Key points Complement has an important physiological role in host immune defences and tissue remodelling. The physiological role of complement extends to the regulation of synaptic development. Complement has a key pathophysiological role in autoimmune neurological diseases and mediates the actions of pathogenic autoantibodies, such as acetylcholine receptor antibodies and aquaporin 4 antibodies. For some autoimmune neurological diseases, such as myasthenia gravis and neuromyelitis optica spectrum disorders, approved complement-targeted treatments are now available. Complement also seems to be of pathogenic relevance in neurodegenerative diseases such as Alzheimer disease, in which innate immune-driven inflammation is receiving increasing attention. The field of complement-targeted therapeutics is rapidly expanding, with several FDA-approved agents and others currently in phase II and phase III clinical trials.

Dataset Information

Extracellular Vesicle-Based Therapeutics in Neurological Disorders.

Publications

Extracellular Vesicle-Based Therapeutics in Neurological Disorders.

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