David Yurek, PhD

Current Research:

Gene Therapy Approach to Reduce Alpha-Synuclein Aggregation in an Animal Model of PD

Principal Investigator at UK:

• David Yurek, PhD Department of Neurosurgery, University of Kentucky

Sub Investigator:

• Caryl E. Sortwell, PhD, Michigan State University
• George Smith, Temple University

Project Summary: The proposed research is a joint project between three academic laboratories (Dr. Yurek, University of Kentucky; Dr. Sortwell, Michigan State University; Dr. Smith, Temple University) in which pre‐clinical studies are designed to study the therapeutic potential of using AAV to overexpress Ras analog in brain 8B (Rab8B) gene in an animal model of Parkinson’s disease (PD). The RAB GTPases are regulators of vesicle‐mediated transport and are thought to be important in the clearance of pathologic alpha‐synuclein (α‐synuclein). We chose to target Rab8B in these studies because it is one member of the RAB GTPases family whose dysregulation or knockdown are associated with increased α‐synuclein aggregation and toxicity in dopaminergic neurons1‐3. We will use an animal PD model in which pathologic alpha‐synuclein pre‐formed fibrils (PFF) are injected into the rat striatum in order to trigger aggregation of oligomerized α‐synuclein fibrils

in nigrostriatal dopamine neurons mimicking Lewy body formation and inducing neurodegeneration. We will inject AAV‐Rab8B into the nigrostriatal pathway of PFF‐treated animals shortly after alpha‐synuclein aggregation begins and look at both the short‐term and long‐term effects of RAB8b overexpression on α‐synuclein aggregation using cellular and molecular techniques to identify α‐synuclein aggregation. We will also use cellular, molecular and behavioral measures to assess the long‐term overexpression of Rab8B on the integrity of the dopamine neurons in the nigrostriatal pathway.

Condition: Parkinson's Disease

Contact: 

• David Yurek, PhD 
  
  Email: dyure00@uky.edu
  
  Phone: (859) 257-8219

Team Members: 

• David Yurek