Targeting Microglial Receptors May Slow ALS Progression

New research identifies a pathway where blocking two receptors in microglia could preserve motor neurons in ALS mouse models.

A study published in *Nature Communications* found that SOD1 G93A mice with microglial deletion of AXL and MER receptors—key TAM signaling proteins—showed slower disease progression than standard models. These mice developed early symptoms 30 days sooner but reached terminal clinical endpoints 3 weeks later, retaining roughly three times as many motor neurons. Human spinal cord tissue from six sporadic ALS patients also revealed significantly elevated expression of these receptors compared to age-matched controls.

The research focuses on how microglia mistakenly target living neurons in ALS, a process linked to the externalization of phosphatidylserine on neurons without cleaved caspase-3 markers. By disrupting this pathway in microglia, the study suggests a potential mechanism to prevent neuron loss. The lead authors—Greg Lemke (Salk Institute) and Youtong Huang—highlighted that targeting TAM receptors could extend healthy lifespan in ALS.

This work moves abundance by revealing a specific biological pathway for intervention. If translated to humans, therapies blocking microglial AXL/MER could preserve motor function longer, directly addressing the need for extended healthy life in ALS. However, the findings are limited to SOD1 G93A mouse models and postmortem human tissue. The August 2026 date noted in the source appears unverified and may reflect a future test timeline.

What to watch: Human trials for TAM receptor modulation in ALS, and whether this pathway applies to other ALS subtypes beyond SOD1 G93A.

Source: Lifespan.io