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阿立莫克莫尔纳米胶束的治疗潜力:对阿尔茨海默病和帕金森病病理学的体外影响及其与体内炎症反应的相关性

Therapeutic Potential of Arimoclomol Nanomicelles: In Vitro Impact on Alzheimer's and Parkinson's Pathology and Correlation with In Vivo Inflammatory Response.

作者信息

Xavier-de-Britto Isabelle, Gomes-da-Silva Natália Cristina, Gomes Soares Marilia Amável, Follmer Cristian, Dabkiewicz David, Alencar Luciana Magalhães Rebelo, Sant'Anna Celso, Ferreira Tatiana Paula Teixeira, Martins Patrícia Machado Rodrigues E Silva, Ricci-Junior Eduardo, Fechine Pierre Basílio Almeida, Santos-Oliveira Ralph

机构信息

Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro, Rio de Janeiro 21941906, Brazil.

Laboratory of Biological Chemistry of Neurodegenerative Disorders, Department of Physical Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.

出版信息

ACS Chem Neurosci. 2025 Feb 19;16(4):699-710. doi: 10.1021/acschemneuro.4c00734. Epub 2025 Feb 5.

Abstract

This study investigates the potential of arimoclomol-loaded nanomicelles for the treatment of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as their anti-inflammatory properties. Arimoclomol, a coinducer of heat shock proteins (HSPs), has shown clinical promise in mitigating protein misfolding, a hallmark of these diseases. In this work, arimoclomol nanomicelles significantly reduced the aggregation of β-amyloid (Aβ) and α-synuclein (α-syn), key pathological proteins in Alzheimer's and Parkinson's. Additionally, the nanomicelles demonstrated potent anti-inflammatory effects, reducing leukocyte and neutrophil counts in an acute inflammation model. These results suggest that arimoclomol nanomicelles could enhance clinical outcomes by targeting both neurodegenerative and inflammatory processes, offering a promising therapeutic strategy for long-term disease management.

摘要

本研究调查了载有阿利克仑莫的纳米胶束用于治疗阿尔茨海默病和帕金森病等神经退行性疾病的潜力及其抗炎特性。阿利克仑莫是热休克蛋白(HSPs)的共诱导剂,在减轻蛋白质错误折叠方面已显示出临床前景,而蛋白质错误折叠是这些疾病的一个标志。在这项工作中,阿利克仑莫纳米胶束显著减少了β-淀粉样蛋白(Aβ)和α-突触核蛋白(α-syn)的聚集,这两种蛋白分别是阿尔茨海默病和帕金森病的关键病理蛋白。此外,纳米胶束还表现出强大的抗炎作用,在急性炎症模型中降低了白细胞和中性粒细胞计数。这些结果表明,阿利克仑莫纳米胶束可以通过针对神经退行性和炎症过程来改善临床结果,为长期疾病管理提供了一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa9/11843614/84fef454d447/cn4c00734_0001.jpg

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