Nat Neurosci exophages may prolong the survival of ALS patients

Small glial cells and exoskeleton macrophages are associated with amyotrophic lateral sclerosis (ALS), although their respective roles have yet to be determined.
the current paper, in mice with ALS models and ALS patients, macrophages along the axons of peripheral motor neurons were found to respond to neurodegenerative.
In the ALS mouse model, cell replacement was used to target gene regulation of reactive oxygen species pathways in exos peritonal bone marrow cells in ALS mice, reducing the activation of exosymperic macrophages and small glial cells, finding delayed symptoms and improving survival.
transcriptional histology studies have shown that sethicular macrophages and small glial cells respond differently to neurodegeneration, with instantaneous changes in macrophages and the aggressive one-way activation of small glial cells.
modified exophages inhibited the reaction of inflammatory small glial cells and turned to neuron support.
, regulating macrophages has the ability to affect disease progress and may have therapeutic value for ALS.
ALS is the most common motor neuron (MN) disease characterized by upper and lower MN degeneration, leading to aggressive paralysis and patient death.
motor neurons in the spinal cord are not common neurons because the body cells in the spinal cord are surrounded by small glial cells, and their axons (which extend around) are surrounded by surrounding macrophages.
because small glial cells (from which the ovopian sacs come from) and exophages have different effects in different environments, the study speculates that they may have different effects on ALS.
the experiment first found that in the SOD1 G37R ALS mouse model and the SOD1 G93AALS mouse model, macrophages protruding along the axis around MN were activated, and in the following image, The activity of small glial cells and peripheral macrophages in ALS human patients stained the spinal cord with abdominal (motor) and back (sensory) nerve roots and surrounding nerves with small glial/macrophage markers CD68.
found that CD68 plus cells were present in the abdominal corners of the ALS spinal cord and in the peripheral nerves of patients with abdominal roots and ALS, but not in the control group.
Here the ALS mouse model was chosen to assess the effects of exosycient nerve macrophages (independent of small glial cells) on disease, and the (efficient) mutant expression SOD1 exophages were replaced here with macrophages with macrophages with reduced neurotoxic ROS reactions.
, the number of MNs remained unchanged, and at the end of the period, the number of MNs improved only slightly.
this is not enough to increase survival, SOD1 WT /GFP BM transplantation can increase muscle strength.
Next, it was found that replacement during the onset of peripheral neurologic macrophage disease increased survival in ALS mice, but there was no difference in the number of MN and CD3 plus cells in two groups of cell transplanted mice, but in the experiment, a decrease in spinal cord glial cell activation and macrophage activation were observed, and an increase in survival in mice in the experimental group receiving cell transplantation was observed.
Therefore, the timing of peripheral macrophage replacement can be considered to be a key parameter for macrophage regulation, and it is possible to slow the disease process and increase survival in ALS mice by modifying peripheral macrophages.
, RNA sequencing analysis was used to determine the macrophage response of the squire nerve endings in ALS mice during the disease.
analysis of genes that regulate neurologic macrophages shows that the regulatory spectrum is not progressive, but mutated.
is modified between each of the four points in time analyzed, including between the onset and early symptoms and between the early symptoms and the end stage.
small glial cell gene regulation spectrum is one-way (mostly from the beginning of symptoms before the ongoing upward) and carried out.
, macrophages and small glial cells have very different patterns of gene regulation.
below is a heat map of genes regulated by neurophages and small glial cells.
In summary, modifying peripheral macrophages can reduce inflammation around the nerve and the central nervous system, and peripheral macrophages can affect the progression of the disease and survival of alS mouse models, so it is believed that regulating peripheral macrophages may have therapeutic value in ALS patients.
: Aude Chiot, Sakina Zaïdi, et al. Modifying macrophages at the periphery has the capacity to change microglial reactivity and to extend ALS survival. Nature Neuroscience (2020) DOI:10.1038/s41593-020-00718-zShiqi Zhang Source: MedSci Original Copyright Notice: All noted on this website : The text, images and audio and video materials of Mets Medicine or Source: MedSci Originals are owned by Metz Medicine and may not be reproduced by any media, website or individual without authorization, and shall be reproduced with the words "Source: Mets Medicine".
all reprinted articles on this website are for the purpose of transmitting more information and clearly indicate the source and author, and media or individuals who do not wish to be reproduced may contact us and we will delete them immediately.
at the same time reproduced content does not represent the position of this site.
leave a message here