Stathmin-2 (STMN2) is a target of the ALS-protein TDP-43 suggesting that loss of STMN2 due to TDP-43 pathology could contribute to the development of ALS. However, no studies in animals had tested the function of STMN2. Kelsey Krus, an MD/PhD student in the lab, made a STMN2 mouse model and discovered that even modest reductions in STMN2 […]
Category: Publication Announcement
Activating Mutations of Sarm1 Enriched in ALS
Sarm1 mutations are not common in ALS patients, but a careful examination of the ones that do occur by Dr. Joseph Bloom and colleagues has shown that they tend to cause Sarm1 to be constitutively active and occur more frequently in ALS patients than in the general population. This research, published in Molecular Neurodegeneration, suggests […]
Discovery of SARM1 Activation by Allosteric Metabolite Sensing Described in New Neuron Paper
SARM1 is the key executioner enzyme for axon degeneration. In a healthy neuron, SARM1 exists in an enzymatically “off” state. Axon injury turns on SARM1’s activity to hydrolyze the important metabolite NAD+, leading to metabolic crisis and axon fragmentation. The mechanism underlying SARM1 activation by axon injury was discovered in a recent study from the […]
New PNAS Paper Examines Mechanism of Sarm1 Autoinhibition
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 […]
Examining the Role of SARM1 in a Mouse Model of Glaucoma
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.
Mechanistically Distinct Chemotherapeutics Cause CIPN via Sarm1
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, […]
DLK responsible for many Fragile X phenotypes in a fly model
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 […]
DiAntonio/Milbrandt labs’ discovery helps solve a 20 year mystery
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 […]
A Big Picture Review of Recent Developments
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 […]
Read about Highwire’s interaction with dNMNAT in EMBO Reports
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.
Gene therapy for peripheral neuropathy successful in mice
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.
Read all about it — Hsp90’s role in axon injury signalling
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.
New paper in PNAS
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.