Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.
Canavan Disease as a Model for Gene Therapy-Mediated Myelin Repair.
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DOI：
10.3389/fncel.2021.661928
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发表时间：
2021
影响因子：
5.3
通讯作者：
Gao G
中科院分区：
文献类型：
--
作者：
Lotun A;Gessler DJ;Gao G
近年来，罕见的遗传性中枢神经系统（CNS）疾病（如白质营养不良症或白质紊乱）的科学和治疗领域已经显著扩大，部分原因是细胞和临床筛查的技术进步，以及使用基因治疗等新技术的补救疗法。然而，由于神经胶质异常的先天和可变影响，旨在使与白质营养不良相关的病理改变正常化的治疗尤其复杂，这可能导致发育性髓鞘形成的大规模功能缺陷，从而导致下游神经元损伤。在过去二十年的新兴研究中，胶质细胞，特别是少突胶质细胞和星形胶质细胞，在构建和维持髓磷脂功能和神经元活力方面发挥了关键的调节作用。考虑到髓磷脂形成在大脑发育中的重要性，髓磷脂修复以一种时间依赖性的方式对诊断为白质疾病的患者的中枢神经系统恢复稳态功能至关重要。本文以Canavan病（CD）为脑白质营养不良模型，回顾了脑中最丰富的氨基酸衍生物n -乙酰天冬氨酸（NAA）在Canavan病CNS髓鞘化病理中的假设作用，并讨论了星形胶质细胞在CD和其他脑白质营养不良的时间敏感性疾病纠正中的可能功能。通过这一分析，我们还强调了基因治疗对其他白质营养不良的潜在益处，其中替代中枢神经系统细胞靶向白质疾病可能是一种适用的修复治疗途径。
In recent years, the scientific and therapeutic fields for rare, genetic central nervous system (CNS) diseases such as leukodystrophies, or white matter disorders, have expanded significantly in part due to technological advancements in cellular and clinical screenings as well as remedial therapies using novel techniques such as gene therapy. However, treatments aimed at normalizing the pathological changes associated with leukodystrophies have especially been complicated due to the innate and variable effects of glial abnormalities, which can cause large-scale functional deficits in developmental myelination and thus lead to downstream neuronal impairment. Emerging research in the past two decades have depicted glial cells, particularly oligodendrocytes and astrocytes, as key, regulatory modulators in constructing and maintaining myelin function and neuronal viability. Given the significance of myelin formation in the developing brain, myelin repair in a time-dependent fashion is critical in restoring homeostatic functionality to the CNS of patients diagnosed with white matter disorders. Using Canavan Disease (CD) as a leukodystrophy model, here we review the hypothetical roles of N-acetylaspartate (NAA), one of the brain's most abundant amino acid derivatives, in Canavan disease's CNS myelinating pathology, as well as discuss the possible functions astrocytes serve in both CD and other leukodystrophies' time-sensitive disease correction. Through this analysis, we also highlight the potential remyelinating benefits of gene therapy for other leukodystrophies in which alternative CNS cell targeting for white matter disorders may be an applicable path for reparative treatment.
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DOI：
10.1038/mt.2008.166
发表时间：
2008-10
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
Best S;Wou K;Vora N;Van der Veyver IB;Wapner R;Chitty LS
通讯作者：
Chitty LS
影响因子：
2.5
作者：
Alisky, JM;Hughes, SM;Davidson, BL
通讯作者：
Davidson, BL
DOI：
10.1016/0005-2760(68)90101-x
发表时间：
1968-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
BENUCK, M;DADAMO, AF
通讯作者：
DADAMO, AF
影响因子：
2.9
作者：
Ariyannur, Prasanth S.;Moffett, John R.;Namboodiri, Aryan M. A.
通讯作者：
Namboodiri, Aryan M. A.