Microglia kills motor neurons in ALS through MERKT receptors

Researchers have identified the cellular mechanism by which microglia—immune cells of the brain—accelerates motor neuron death in amyotrophic lateral sclerosis (ALS). In SOD1G93A mouse models, inactivation of TAM receptor tyrosine kinases (Axl and Merkt) significantly extends lifespan and preserves both cholinergic neurons and neuromuscular synapses. The team discovered that neuronal surfaces in these mice express elevated levels of phosphatidylserine, a potent "eat-me" signal that triggers microglial phagocytosis. In affected spinal cords, microglial lysosomes are filled with debris from living cholinergic neurons—accumulation that drops sharply when Axl and Merkt genes are deleted. This finding reframes the therapeutic target: beyond TDP-43 aggregation, it points to suppressing the microglial appetite for phagocytosis itself. For biohackers and clinicians tracking longevity interventions, it opens a path toward selective TAM receptor modulators as candidates for human ALS trials.