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引用次数: 0
摘要
肌萎缩性脊髓侧索硬化症(ALS)是一种神经退行性疾病,主要导致运动神经元变性。传统的研究重点是以运动神经元为中心的机制,最近已转向了解小胶质细胞等非神经元细胞在 ALS 病理生理学中的作用。诱导多能干细胞(iPSC)技术的进步使人们能够生成 iPSC 衍生的小胶质细胞单培养物和共培养物,以研究它们在 ALS 发病机制中的作用。在此,我们简要回顾了这些研究对小胶质细胞在 ALS 中作用的见解。iPSC 衍生的小胶质细胞单培养物揭示了 ALS 相关突变导致的内在细胞功能障碍,而小胶质细胞-运动神经元共培养研究则证明了突变小胶质细胞对运动神经元的神经毒性作用。基于这些发现,我们简要讨论了目前尚未解决的问题以及如何在未来的研究中解决这些问题。iPSC 模型有望揭示 ALS 的疾病相关通路并确定潜在的治疗靶点。
Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.
期刊介绍:
molecular – cellular – biomedical – physiology – translational research – systems - hypotheses encouraged
BioEssays is a peer-reviewed, review-and-discussion journal. Our aims are to publish novel insights, forward-looking reviews and commentaries in contemporary biology with a molecular, genetic, cellular, or physiological dimension, and serve as a discussion forum for new ideas in these areas. An additional goal is to encourage transdisciplinarity and integrative biology in the context of organismal studies, systems approaches, through to ecosystems, where appropriate.