91小黄车

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鈥恈linical 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鈥檚 disease (PD). The RAB GTPases are regulators of vesicle鈥恗ediated transport and are thought to be important in the clearance of pathologic alpha鈥恠ynuclein (伪鈥恠ynuclein). 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 伪鈥恠ynuclein aggregation and toxicity in dopaminergic neurons1鈥�3. We will use an animal PD model in which pathologic alpha鈥恠ynuclein pre鈥恌ormed fibrils (PFF) are injected into the rat striatum in order to trigger aggregation of oligomerized 伪鈥恠ynuclein fibrils

in nigrostriatal dopamine neurons mimicking Lewy body formation and inducing neurodegeneration. We will inject AAV鈥怰ab8B into the nigrostriatal pathway of PFF鈥恡reated animals shortly after alpha鈥恠ynuclein aggregation begins and look at both the short鈥恡erm and long鈥恡erm effects of RAB8b overexpression on 伪鈥恠ynuclein aggregation using cellular and molecular techniques to identify 伪鈥恠ynuclein aggregation. We will also use cellular, molecular and behavioral measures to assess the long鈥恡erm 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