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解码神经疾病的基因蓝图:疾病机制与突破性基因疗法

Decoding the genetic blueprints of neurological disorders: disease mechanisms and breakthrough gene therapies.

作者信息

Saeed Umar, Piracha Zahra Zahid, Tariq Muhammad Nouman, Syed Shayan, Rauf Maria, Razaq Laiba, Iftikhar Muhammad Kaleem, Maqsood Amna, Ahsan Syed Muhammad

机构信息

Operational Research Center in Healthcare, Near East University, Nicosia, Türkiye.

Foundation University School of Health Sciences (FUSH), Foundation University Islamabad, Islamabad, Pakistan.

出版信息

Front Neurol. 2025 Apr 11;16:1422707. doi: 10.3389/fneur.2025.1422707. eCollection 2025.

DOI:10.3389/fneur.2025.1422707
PMID:40291849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12022314/
Abstract

Neurological disorders pose a rapidly growing global health burden, significantly affecting cognitive and motor functions with profound societal repercussions. This comprehensive review probe into the genetic foundations of various neurological conditions while exploring innovative RNA-based therapeutics particularly gene therapies as cutting edge treatment strategies. Through an in-depth analysis of existing literature, the study examines the genetic landscape, disease mechanisms, and gene-based intervention possibilities across a range of neurological disorders, including Cerebellar Ataxias, Autosomal Recessive Ataxia, Mitochondrial Cerebellar Ataxia, Multiple System Atrophy (MSA), Idiopathic Late-Onset Cerebellar Ataxia, Hereditary Spastic Paraplegias, Alzheimer's Disease, Vascular Dementia, Lewy Body Dementia, Frontotemporal Dementias, Inherited Prion Diseases, and Huntington's Disease. It uncovers the intricate network of genetic mutations driving these disorders, shedding light on their mechanisms and uncovering promising therapeutic targets. The review also highlights the remarkable potential of RNA-based therapeutics, with gene therapies standing at the forefront of precision treatment approaches. By offering an up-to-date understanding of the genetic intricacies and emerging therapeutic possibilities in neurological disorders, this study significantly contributes to the advancement of precision medicine in neurology. It also paves the way for future research and clinical applications aimed at improving patient care and outcomes.

摘要

神经疾病给全球健康带来的负担正迅速增长,严重影响认知和运动功能,产生深远的社会影响。这篇全面综述探究了各种神经疾病的遗传基础,同时探索了基于RNA的创新疗法,尤其是作为前沿治疗策略的基因疗法。通过对现有文献的深入分析,该研究考察了一系列神经疾病的遗传格局、疾病机制以及基于基因的干预可能性,这些疾病包括小脑共济失调、常染色体隐性共济失调、线粒体小脑共济失调、多系统萎缩(MSA)、特发性迟发性小脑共济失调、遗传性痉挛性截瘫、阿尔茨海默病、血管性痴呆、路易体痴呆、额颞叶痴呆、遗传性朊病毒病和亨廷顿舞蹈症。它揭示了导致这些疾病的复杂基因突变网络,阐明了其机制并发现了有前景的治疗靶点。该综述还强调了基于RNA疗法的巨大潜力,基因疗法处于精准治疗方法的前沿。通过提供对神经疾病遗传复杂性和新兴治疗可能性的最新理解,这项研究极大地推动了神经学精准医学的发展。它还为旨在改善患者护理和治疗结果的未来研究及临床应用铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/57af87cec616/fneur-16-1422707-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/eee7b768d2c5/fneur-16-1422707-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/6fef5d1df06a/fneur-16-1422707-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/57af87cec616/fneur-16-1422707-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/eee7b768d2c5/fneur-16-1422707-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/6fef5d1df06a/fneur-16-1422707-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6392/12022314/57af87cec616/fneur-16-1422707-g003.jpg

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本文引用的文献

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Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.脊髓小脑性共济失调 4 型是由 ZFHX3 基因中的 GGC 扩展引起的,与明显的自主神经功能障碍和运动神经元体征有关。
J Intern Med. 2024 Sep;296(3):234-248. doi: 10.1111/joim.13815. Epub 2024 Jul 7.
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Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy.基于 CRISPR 的基因编辑技术综述:机制、挑战及在癌症治疗中的应用。
Mol Cancer. 2024 Jan 9;23(1):9. doi: 10.1186/s12943-023-01925-5.
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基于纳米生物材料的增强脑靶向递药策略用于神经退行性疾病治疗的研究进展。
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Advances in Neurodegenerative Diseases.神经退行性疾病的进展
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