Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy.
Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy.
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DOI：
10.1186/s40478-020-01093-3
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发表时间：
2020-12-07
影响因子：
7.1
通讯作者：
Harris RA
中科院分区：
文献类型：
--
作者：
Han J;Sarlus H;Wszolek ZK;Karrenbauer VD;Harris RA
CSF1R相关脑白质病是由集落刺激因子1受体（CSF1R）基因突变引起的一种伴轴突球体和色素胶质的成人发病脑白质病。这种疾病在全球分布，目前尚无治愈方法。csf1r相关脑白质病患者的临床症状各不相同，包括认知障碍、进行性神经精神和运动症状。CSF1R主要在中枢神经系统（CNS）的小胶质细胞上表达，因此CSF1R相关的脑白质病现在被归类为中枢神经系统原发性小胶质病。使用基于小胶质细胞的免疫疗法可以潜在地解决这一迫切的未满足的医疗需求。随着近年来实验小胶质研究领域的快速发展，人们正在研究通过条件遗传方法或药物治疗（CSF1R抑制剂）来替代小胶质细胞耗竭后的空白小胶质细胞生态位。此外，造血干细胞移植为交换功能失调的小胶质细胞提供了一种新兴手段，目的是减少脑病变，缓解临床症状，延长csf1r相关白质脑病患者的生命。本文综述了小胶质细胞生物学和csf1r相关脑白质病的最新进展。通过替代小胶质细胞来改善csf1r相关白质脑病患者生活质量的潜在治疗策略将被提出。
CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms. CSF1R is predominantly expressed on microglia within the central nervous system (CNS), and thus CSF1R-related leukoencephalopathy is now classified as a CNS primary microgliopathy. This urgent unmet medical need could potentially be addressed by using microglia-based immunotherapies. With the rapid recent progress in the experimental microglial research field, the replacement of an empty microglial niche following microglial depletion through either conditional genetic approaches or pharmacological therapies (CSF1R inhibitors) is being studied. Furthermore, hematopoietic stem cell transplantation offers an emerging means of exchanging dysfunctional microglia with the aim of reducing brain lesions, relieving clinical symptoms and prolonging the life of patients with CSF1R-related leukoencephalopathy. This review article introduces recent advances in microglial biology and CSF1R-related leukoencephalopathy. Potential therapeutic strategies by replacing microglia in order to improve the quality of life of CSF1R-related leukoencephalopathy patients will be presented.
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耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
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12.7
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影响因子：
8.8
作者：
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Wolf, Susanne A.
影响因子：
14.5
作者：
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通讯作者：
Mannis, Gabriel N.
影响因子：
16.2
作者：
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通讯作者：
Barres BA