| Start Date: | 3/7/2014 | Start Time: | 4:00 PM |
| End Date: | 3/7/2014 | End Time: | 5:30 PM |
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Event Description
Krista Spiller, PhD, postdoctoral fellow at the University of Pennsylvania, will discuss how, even though mutant proteins are broadly expressed in neurodegenerative diseases, only some neuronal subsets are vulnerable. In patients with amyotrophic lateral sclerosis (ALS), most motor neurons degenerate but those innervating extraocular muscles, pelvic sphincters and slow limb muscles exhibit selective resistance. We thus examined these pools in order to understand mechanisms of selective vulnerability to neurodegeneration. We identified 18 genes that show >10-fold differential expression between resistant and vulnerable motor neurons. One of these, matrix metalloproteinase-9 (MMP-9), is expressed only by fast motor neurons, which are selectively vulnerable. In ALS model mice expressing mutant superoxide dismutase (SOD1), reduction of MMP-9 function using gene ablation, viral gene therapy, or pharmacological inhibition significantly delayed muscle denervation. These studies suggest that MMP-9 is a promising candidate therapeutic target for ALS and also support the study of neuronal diversity as a potential way to define novel therapeutic strategies for the treatment of neurodegenerative diseases. |
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Location:
Papadakis Integrated Sciences Building (PISB), Room 120, located at the corner of 33rd and Chestnut Streets. |
Audience:
AlumniCurrent StudentsFacultyProspective StudentsPublicStaff |
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