2024 Glia 72(7):1319–1339
Chronically activated microglia in ALS gradually lose their immune functions and develop unconventional proteome
Authors: Barreto-Núñez R, Béland LC, Boutej H, Picher-Martel V, Dupré N, Barbeito L, Kriz J
Why it matters
Characterizes microglia across disease stages in the SOD1-G93A model of ALS. In advanced disease, microglia showed reduced phagocytic capacity, a diminished response to innate immune challenge and an unconventional protein signature — supporting the view that chronically activated microglia become functionally inefficient immune cells rather than simply “over-inflamed”.
2024 Molecular Therapy 32(3):783–799
Targeting SRSF3 restores immune mRNA translation in microglia/macrophages following cerebral ischemia
Authors: Rahimian R, Guruswamy R, Boutej H, Cordeau P Jr, Weng YC, Kriz J
Why it matters
Extends the SRSF3 checkpoint to sterile inflammation after experimental stroke. Highly upregulated immune mRNAs were again not translated, and phosphorylated SRSF3 rose in microglia/macrophages. Intranasal SRSF3-directed siRNA alleviated translational arrest of selected immune genes, induced de novo synthesis of immune proteins and was associated with smaller ischemic lesions in mice.
2020 Brain Communications 2(2):fcaa124
Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses
Authors: Béland LC, Markovinovic A, Jakovac H, De Marchi F, Bilic E, Mazzini L, Kriz J, Munitic I
Why it matters
A review framing ALS immunity beyond “too much inflammation”, discussing how excessive inflammation and inefficient immune responses can coexist — the conceptual backdrop for restoring, rather than simply suppressing, innate immune function.
2017 Cell Reports 21(11):3220–3233
Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts
Authors: Boutej H, Rahimian R, Thammisetty SS, Béland LC, Lalancette-Hébert M, Kriz J
Why it matters
The founding discovery. By profiling ribosome-bound mRNAs and newly made peptides in microglia in vivo, the study found that the most highly upregulated innate immune transcripts were not translated after immune challenge. This selective, 3′UTR-mediated repression involved the RNA-binding protein SRSF3, and SRSF3 knockdown released translation of several immune proteins.
2016 Journal of Neuroscience 36(3):1031–1048
IL-10 Controls Early Microglial Phenotypes and Disease Onset in ALS Caused by Misfolded Superoxide Dismutase 1
Authors: Gravel M, Béland LC, Soucy G, Abdelhamid E, Rahimian R, Gravel C, Kriz J
Why it matters
Earlier foundational work on microglial states in ALS models, describing an adaptive shift in microglial phenotypes in preclinical stages of SOD1-mediated disease and a role for IL-10 in controlling early microglial responses and disease onset.