Clearance of neuronal debris in the CNS is an important function of microglia, both during normal neurogenic processes and following injury. According to a paper in the April 6 Nature led by Greg Lemke at the Salk Institute in La Jolla, CA, two TAM receptor tyrosine kinases called Mer and Axl are expressed in microglia and regulate this critical phagocytic function. Mice lacking these receptors not only failed to clear cellular debris in neurogenic regions of the brain, but also exhibited marked accumulation of new neurons in the olfactory bulb, suggesting that microglia may engulf a subset of compromised newborn neurons prior to apoptosis. Surprisingly, in a mouse model of Parkinson’s disease, Axl expression was elevated, and deletion of Mer and Axl increased lifespan, suggesting that in the diseased brain, TAM receptors may cause excessive clearance of unhealthy neurons and thereby exacerbate disease. Further work is needed to characterize the role of these microglial receptors in other neurodegenerative diseases, including ALS.
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Fourgeaud L, Través PG, Tufail Y, Leal-Bailey H, Lew ED, Burrola PG, Callaway P, Zagórska A, Rothlin CV, Nimmerjahn A, Lemke G. TAM receptors regulate multiple features of microglial physiology. Nature. 2016 Apr 6. [Pubmed].