Related Experiment Video
Updated: Apr 26, 2026
Rapid and Refined CD11b Magnetic Isolation of Primary Microglia with Enhanced Purity and Versatility
Published on: April 13, 2017
The role of microglia in human disease: therapeutic tool or target?
Nathalie Cartier1, Coral-Ann Lewis, Regan Zhang
1INSERM U986, 80 rue du Général Leclerc, 94276, Le Kremlin-Bicêtre, France.
Abstract:
Microglia have long been the focus of much attention due to their strong proliferative response (microgliosis) to essentially any kind of damage to the CNS. More recently, we reached the realization that these cells play specific roles in determining progression and outcomes of essentially all CNS disease. Thus, microglia has ceased to be viewed as an accessory to underlying pathologies and has now taken center stage as a therapeutic target. Here, we review how our understanding of microglia's involvement in promoting or limiting the pathogenesis of diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, multiple sclerosis, X-linked adrenoleukodystrophy (X-ALD) and lysosomal storage diseases (LSD) has changed over time. While strategies to suppress the deleterious and promote the virtuous functions of microglia will undoubtedly be forthcoming, replacement of these cells has already proven its usefulness in a clinical setting. Over the past few years, we have reached the realization that microglia have a developmental origin that is distinct from that of bone marrow-derived myelomonocytic cells. Nevertheless, microglia can be replaced, in specific situations, by the progeny of hematopoietic stem cells (HSCs), pointing to a strategy to engineer the CNS environment through the transplantation of modified HSCs. Thus, microglia replacement has been successfully exploited to deliver therapeutics to the CNS in human diseases such as X-ALD and LSD. With this outlook in mind, we will discuss the evidence existing so far for microglial involvement in the pathogenesis and the therapy of specific CNS disease.
Insights
Microglia are central to CNS diseases, acting as therapeutic targets. Replacing these cells with hematopoietic stem cells offers a promising treatment strategy for conditions like X-linked adrenoleukodystrophy and lysosomal storage diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), exhibit a robust proliferative response (microgliosis) to CNS damage.
- Emerging evidence highlights microglia's critical roles in the progression and outcomes of various CNS diseases, shifting their perception from passive bystanders to key players.
- Microglia are now recognized as significant therapeutic targets for neurological disorders.
Purpose of the Study:
- To review the evolving understanding of microglia's role in the pathogenesis of CNS diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, multiple sclerosis, X-linked adrenoleukodystrophy (X-ALD), and lysosomal storage diseases (LSD).
- To explore the therapeutic potential of microglia replacement strategies, particularly through hematopoietic stem cell (HSC) transplantation, for CNS diseases.
Main Methods:
- Literature review of studies investigating microglial involvement in CNS disease pathogenesis.
- Analysis of research on microglia replacement therapies and their clinical applications.
Main Results:
- Microglia's functions can be both detrimental and beneficial in CNS disease pathogenesis.
- Microglia have a distinct developmental origin but can be replaced by HSC progeny.
- Microglia replacement via HSC transplantation has shown clinical success in treating X-ALD and LSD.
Conclusions:
- Microglia are pivotal in CNS disease progression and represent a key therapeutic target.
- Microglia replacement by HSC transplantation is a viable strategy for engineering the CNS environment and delivering therapeutics.
- Targeting microglial functions and employing replacement strategies hold significant promise for treating a range of CNS disorders.
More Related Videos
06:12Author Spotlight: Induced Microglia-Like Cell Technology to Shed Light on the Role of Microglial Dysfunction in Neuropsychiatric Disorders
Published on: September 6, 2024
05:35Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
