Neurodegenerative Diseases Discussion Group
Chasing the Axon's End
Posted January 13, 2010
Long regarded as unyielding territory by neurobiologists and neurologists alike, the capacity of the adult central nervous system (CNS) for growth is at last being revealed, along with its limitations. At a March 20, 2006, Academy meeting, three scientists discussed the failure and capability of adult CNS axons to sprout and to grow after injury, as well as developmental processes that govern axonal growth.
Stephen Strittmatter described the roles of the Nogo protein and its receptor in restricting adult CNS plasticity and regeneration. The protein may prevent axonal growth following critical periods of nervous system development. Glenn Yiu reviewed signaling mechanisms related to the Nogo system. Christopher Henderson discussed the influence of a growth factor called glial cell line-derived neurotrophic factor (GDNF) on motor neuron axonal growth during development in one specific system.
Use the tabs above to find a meeting report and multimedia from this event.
Motor Neuron Center
The Motor Neuron Center at Columbia University aims to strengthen interactions between basic scientists and clinicians on the campus interested in the motor neuron diseases ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy).
National Institute for Neurological Disorders and Stroke
An overview of spinal cord injury, including information on axon damage.
National Spinal Cord Injury Association
Read more about different approaches being used in the search for treatments and cures for spinal cord injury, including axon regeneration.
The Nogo Receptor in Adult CNS Plasticity and Regeneration
Hu, F., B. P. Liu, S. Budel, et al. 2005. Nogo-A interacts with the Nogo-66 receptor through multiple sites to create an isoform-selective subnanomolar agonist. J. Neurosci. 25: 5298-5304. FULL TEXT
Li, S., J. E. Kim, S. Budel, et al. 2005. Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury. Mol. Cell. Neurosci. 29: 26-39.
Li, S., B. P. Liu, S. Budel, et al. 2004. Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J. Neurosci. 24: 10511-10520. FULL TEXT
McGee, A. W., Y. Yang, Q. S. Fischer, et al. 2005. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science 309: 2222-2226.
Inhibited Axon Growth in Adult CNS: Down the Road to Rho
Koprivica, V., K. S. Cho, J. B. Park, et al. 2005. EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science 310: 106-110.
Park, J. B., G. Yiu, S. Kaneko, et al. 2005. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron 45: 345-351.
Yiu, G. & Z. He. 2003. Signaling mechanisms of the myelin inhibitors of axon regeneration. Curr. Opin. Neurobiol. 13: 545-551.
Motor Axon Growth: Inside and Out
Helmbacher, F., E. Dessaud, S. Arber, et al. 2003. Met signaling is required for recruitment of motor neurons to PEA3-positive motor pools. Neuron 39: 767-777.
Henderson, C. E., Y. Yamamoto, J. Livet, et al. 1998. Role of neurotrophic factors in motoneuron development. J. Physiol. Paris 92: 279-281.
Livet, J., M. Sigrist, S. Stroebel, et al. 2002. ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron 35: 877-892.
Stephen Strittmatter, MD, PhD
Stephen Strittmatter is Vincent Coates Professor of Neurology at the Yale University School of Medicine. He studies the molecular basis of axonal extension during development and in the adult central nervous system, and is searching for genes that are induced in successful regeneration in the peripheral nervous system. His group has identified the myelin-derived inhibitory protein, Nogo, and its receptor as inhibitors of axonal regeneration after injury, and is using various methods to identify antagonists to this system that might have regenerative efficacy following spinal cord trauma and stroke.
Strittmatter earned his MD and PhD (pharmacology) at Johns Hopkins University. Following graduation he worked as an intern in medicine and a resident in neurology at Massachusetts General Hospital, and as a clinical and research fellow at Mass. General and Harvard Medical School.
Glenn Yiu, PhD
Glenn Yiu recently completed his PhD at the Children's Hospital Boston and Harvard Medical School, and is now pursuing his MD. As an undergraduate, he majored in biochemistry and psychology at Columbia University. During that time, he also studied synapsin function with Paul Greengard from The Rockefeller University, and developed a deconvolution technique for two-photon imaging with Rafael Yuste at Columbia. He joined Harvard Medical School in 2000, where he has worked with Zhigang He to study the signaling mechanisms that limit axon regeneration in the adult CNS.
Christopher Henderson, PhD
Chris Henderson is a professor at the Columbia University Center for Neurobiology and Behavior. In addition to establishing his own laboratory there in 2005, he helped to found a new Motor Neuron Center, which brings together basic scientists and clinicians to study ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). By studying purified motor neurons in culture, his group has identified polypeptide neurotrophic factors required for motor neuron survival and compounds that can enhance neuronal survival or axon growth. He is seeking not only the genes and chemicals that can affect motor neuron development, growth, and death, but also methods that could serve as a basis for future therapeutic strategies.
Alisa G. Woods
Alisa G. Woods, PhD, is a neurobiologist, biomedical communications consultant, and Adjunct Professor of Psychology at Iona College.