从克拉伯病的病理机制到前沿疗法:全面回顾。

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-03-06 DOI:10.1111/neup.12967
Imen Ketata, Emna Ellouz
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引用次数: 0

摘要

自从克努德-克拉伯(Knud Krabbe)于 1916 年首次记录克拉伯病(KD)以来,直到 GALC 基因突变被确认之前,已有大量研究对克拉伯病(KD)的特征进行了仔细研究。为此,我们研究了 KD 长达八十年的自然史,以深入了解其机制的演变轨迹。通过全面分析,我们发现了涉及该病微观病理机制的分子生物学新元素。这篇综述从一个最新的角度阐述了 KD 的代谢紊乱。最近,细胞外囊泡(EVs)、自噬功能障碍和α-突触核蛋白已成为神经病理过程中的关键因素。EVs可能是一种细胞机制,可避免或减轻过量有毒精神氨酸的有害影响,而提取EVs可能会导致突触功能障碍。研究发现,自噬损伤与精神卫生碱无关,而依赖于 AKT 和 B 细胞淋巴瘤 2。此外,α-突触核蛋白已被认为可诱导细胞死亡和常见生物通路的功能障碍。我们的目标是评估先进疗法在治疗这一特殊疾病方面的有效性。虽然造血干细胞一直是一种主要的治疗方法,但事实证明,特别是在无症状阶段,使用造血干细胞具有挑战性。在这篇综述中,我们汇编了10多项治疗试验的信息,并根据其利弊进行了比较。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
From pathological mechanisms in Krabbe disease to cutting-edge therapy: A comprehensive review.

Since its initial documentation by Knud Krabbe in 1916, numerous studies have scrutinized the characteristics of Krabbe disease (KD) until the identification of the mutation in the GALC gene. In alignment with that, we investigated the natural history of KD spanning eight decades to gain a deeper understanding of the evolutionary trajectory of its mechanisms. Through our comprehensive analysis, we unearthed additional novel elements in molecular biology involving the micropathological mechanism of the disease. This review offers an updated perspective on the metabolic disorder that defines KD. Recently, extracellular vesicles (EVs), autophagy impairment, and α-synuclein have emerged as pivotal players in the neuropathological processes. EVs might serve as a cellular mechanism to avoid or alleviate the detrimental impacts of excessive toxic psychosine levels, and extracting EVs could contribute to synapse dysfunction. Autophagy impairment was found to be independent of psychosine and reliant on AKT and B-cell lymphoma 2. Additionally, α-synuclein has been recognized for inducing cellular death and dysfunction in common biological pathways. Our objective is to assess the effectiveness of advanced therapies in addressing this particular condition. While hematopoietic stem cells have been a primary treatment, its administration proves challenging, particularly in the presymptomatic phase. In this review, we have compiled information from over 10 therapy trials, comparing them based on their benefits and disadvantage.

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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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