Neuronal Intrinsic Signaling for Neuroprotection and Axon Regeneration

Summary

Axonopathy is a typical early characteristic of neurodegenerative diseases in central nervous system (CNS), which leads to axon degeneration and retrograde neuronal cell death. It is critical to decipher the upstream signals that trigger the neurodegeneration cascade to minimize the severe consequences of progressive CNS dysfunction. It is also upmost interest to promote CNS axon regeneration for neural repair. Optic neuropathies are a group of retinal ganglion cell (RGC) diseases with features of axonopathy: they are initiated by optic nerve (ON) injury and that produces secondary RGC death. Prof. Hu’s study of three in vivo mouse models of optic neuropathies (traumatic optic nerve injury, glaucoma and EAE/optic neuritis) revealed that both acute traumatic injury and chronic insult of ON induce endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) signal transduction pathways in RGCs. Modulation of two key downstream pathways of ER stress synergistically promote survival of both RGC somata and axons in all three optic neuropathy models, suggest that neuronal ER stress is a general upstream mechanism for both events in CNS axonopathies, and that axon injury-induced ER stress is the link between the sequential events of axon injury and neuronal soma death. Using the same model, we also revealed a complex neuron-intrinsic balancing mechanism involving AKT as the nodal point of PI3K, mTORC1/2 and GSK3β that coordinates both positive and negative cues to regulate adult CNS axon regeneration.

Speaker - Professor Hu Yang

Prof. Hu, Assistant Professor of Ophthalmology at Stanford

University School of Medicine, is also member of Bio-X

and of Stanford Neurosciences Institute. He received the

Doughlas Johnson Award for Glaucoma Research (2013)

and the Knight Templar Eye Foundation Travel Fellowship

Award (2016). Prof. Hu received his Ph.D in Neuroscience

at Weill Medical College of Cornell University and MD from

Beijing Medical University.

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