Kimura K, Subramanian A, Yin Z, Khalilnezhad A, Wu Y, He D, Dixon KO, Chitta UK, Ding X, Adhikari N, Guzchenko I, Zhang X, Tang R, Pertel T, Myers SA, Aastha A, Nomura M, Eskandari-Sedighi G, Singh V, Liu L, Lambden C, Kleemann KL, Gupta N, Barry JL, Durao A, Cheng Y, Silveira S, Zhang H, Suhail A, Delorey T, Rozenblatt-Rosen O, Freeman GJ, Selkoe DJ, Weiner HL, Blurton-Jones M, Cruchaga C, Regev A, Suvà ML, Butovsky O, Kuchroo VK. Immune checkpoint TIM-3 regulates microglia and Alzheimer's disease. Nature. 2025 May;641(8063):718-731. Epub 2025 Apr 9 PubMed.
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Washington University
I think the findings from the Butovsky and Kuchroo labs regarding TIM-3 are clear, interesting, and important. It definitely appears to be a checkpoint molecule important in mediating microglial homeostasis through TGFβ signaling. From a translational perspective in regard to Alzheimer’s disease, it would seem that turning down TIM-3 during the preclinical phase of AD when there is amyloid pathology developing and little tau pathology is worth looking into in regard to targeting. However, further studies will be needed to assess the role of TIM-3 during the neurodegeneration phase of AD (the symptomatic phase) when more clearcut synaptic and neuron loss is occurring.
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