Axons contain a protein, Sarm1, capable of triggering their self-destruction. It is crucial that such a protein be kept in an ‘off’ state or neurodegeneration will occur. In the current paper from the DiAntonio and Milbrandt labs at Washington University and the Hao Wu lab at Harvard University, Multiple domain interfaces mediate SARM1 autoinhibition, they […]
A recent JCB paper from postdoc Kwang Woo Ko looks at Sarm1’s role in glaucoma. He shows that knocking out Sarm1 protects retinal ganglion cells and axons in a mouse model of glaucoma. His experiments demonstrate that neuroinflammatory and necroptotic signaling work through SARM1 to drive axon loss.
Previous work by Dr. Stefanie Geisler had shown that axonal damage subsequent to administration of vincristine, a common chemotherapeutic, was a result of a Sarm1-dependent mechanism. In the recent JCI Insight paper titled “Vincristine and bortezomib use distinct upstream mechanisms to activate a common SARM1-dependent axon degeneration program,” Dr. Geisler and colleagues demonstrated that Bortezomib, […]
Exciting new research from Alex Russo is presented this month in Cell Reports in a paper titled Wnd/DLK Is a Critical Target of FMRP Responsible for Neurodevelopmental and Behavior Defects in the Drosophila Model of Fragile X Syndrome. FMRP1 is the gene mutated in Fragile-X syndrome. It functions as a translational repressor that targets many mRNAs. When […]
Biology can be pretty amazing. A grad student in the Milbrandt lab, Kow Essuman, and collaborators at UNC and Colorado State University just published a paper in Science on the role of TIR domains in plants. The DiAntonio and Milbrandt labs study how axons degenerate after injury and in disease. A few years ago the […]
Aaron’s recent review in the journal PAIN synthesizes recent developments in our understanding of axon degeneration and discusses the therapeutic implications. This review also includes an audio recording of him describing the research progress. One of the key discoveries discussed is that Sarm1 is itself an NADase enzyme. Understanding that opens up new possibilities for pharmacological […]
New work from Alex Russo and others looking at the axon protective effects of Highwire’s interaction with dNMNAT will be published soon in EMBO Reports.
A new paper in the Journal of Experimental Medicine details the experiments led by Dr. Stefanie Geisler in collaboration with the Milbrandt and DiAntonio labs to target SARM1 using gene therapy in mice. This is an exciting step towards possible treatments for peripheral neuropathy and other disorders involving axon breakdown.
Scott Karney-Grobe thesis work has been published in the PNAS paper, HSP90 is a chaperone for DLK and is required for axon injury signaling. This is an intriguing new role for Hsp90.
We are proud to announce that Dan Summers, a postdoc with a joint appointment in the DiAntonio and Milbrandt labs, has a new paper in the Proceedings of the National Academy of Sciences journal titled Palmitoylation enables MAPK-dependent proteostasis of axon survival factors.