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Control of Axon Degeneration by the Neuronal Cell Body

Weekly Seminar | Not Open to the Public
Who Should Attend: 


How do some neurons survive a lifetime while others succumb to neurodegeneration? We take a ‘bottom-up’ approach to this question by first understanding the molecules and pathways that control neuronal survival, and then working upstream to ask how cellular stresses including misfolded proteins, physical injury, and loss of neurotrophic support disrupt these pathways to promote degeneration. A particular focus has been on survival of the axon, the long cable-like structures that connect neurons and degenerate earliest in many neurodegenerative diseases. We found that axon degeneration is controlled by bi-directional signaling to and from the cell body, leading us to now ask how the cell body controls the localized death of the axon. We further seek to identify proteins that sense the kind of cellular stresses that are not, in themselves, damaging and determine how these proteins signal within a neuron to promote degeneration. Finally, we are interested how neuronal survival is affected by nearby inflammation, in particular in identifying endogenous protective mechanisms that allow the neuron to withstand chronic low-level inflammation without degenerating. Our ultimate goal is understanding how a neuron reacts to its environment and how environmental stimuli affect the balance between survival and death. In support of these questions we employ a range of molecular, genetic, biochemical, and imaging techniques.

Dr. Simon's Figure


Wang G, Simon DJ, Wu Z, Belsky DM, Heller E, O'Rourke MK, Hertz NT, Molina H, Zhong G, Tessier-Lavigne M, Zhuang X.
Structural plasticity of actin-spectrin membrane skeleton and functional role of actin and spectrin in axon degeneration.
Elife. 2019 May 1;8. pii: e38730. doi: 10.7554/eLife.38730.
Simon DJ, Pitts J, Hertz NT, Yang J, Yamagishi Y, Olsen O, Tešić Mark M, Molina H, Tessier-Lavigne M.
Axon Degeneration Gated by Retrograde Activation of Somatic Pro-apoptotic Signaling.
Cell. 2016 Feb 25;164(5):1031-45. doi: 10.1016/j.cell.2016.01.032. Epub 2016 Feb 18.
Simon DJ, Weimer RM, McLaughlin T, Kallop D, Stanger K, Yang J, O'Leary DD, Hannoush RN, Tessier-Lavigne M.
A caspase cascade regulating developmental axon degeneration.
J Neurosci. 2012 Dec 5;32(49):17540-53. doi: 10.1523/JNEUROSCI.3012-12.2012.


Tuesday, January 28, 2020 - 12:30pm


785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

More Information

Lindsey Echevarria

Conditions & Recovery

Neurodegenerative Diseases icon
Worldwide, 50 million people are living with Alzheimer's and other dementias.

Research Methods: 
Axonal Regeneration