Immune system in the brain is important to recover from motor neuron degeneration in diseases like amyotrophic lateral sclerosis.

‘Microglia, a type of immune cell, is important for cleaning up clumps of misfolded proteins called TDP-43 in the brains of ALS patients.’

"The prevailing view in the field has been that immune system inflammation contributes to the death of neurons in ALS, but this study shows the opposite - that microglia are actually critical for neuronal survival," Lee said. 




The number of microglia cells remained stable in mice with ALS symptoms. However, after the researchers chemically suppressed expression of pathological human TDP-43 in the mice, microglia dramatically proliferated and changed their shape and what genes they expressed.
The researchers were perplexed as to why the microglia did not react automatically to the presence of mutant TDP-43 and how subduing its expression incited microglia to react. "This is still a mystery, but one that we'd very much like to figure out in future studies," Spiller said.
The normally branched microglia retracted their extensions and expanded the size of their main cell bodies. (This rapid change in shape is fairly unique to microglia in the central nervous system, although macrophages, microglia's immune-system counterpart in peripheral parts of the body, are similarly dynamic in their shape shifting.)
The now abundant, remade microglia multiplied by 70 percent after one week and selectively cleared accumulated human TDP-43 from motor neurons. Microglia surround TDP-43-filled neurons and turned on genes to make proteins that help them attach to the sick cells and induce a process called phagocytosis that envelops the mutant proteins for disposal. After the mop up, mice stopped exhibiting motor dysfunction symptoms such as leg clasping and tremors, and they regained their ability to walk and gain weight.
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"The way reactive microglia protect neurons points us towards new ideas for ALS therapies," Spiller said. "For example, we want to know if we can encourage the expansion of microglia in early-stage ALS patients to save their motor neurons."
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Source-Eurekalert