1 / 15

α -synuclein, Lewy Bodies, Prions, and Parkinson’s Disease

α -synuclein, Lewy Bodies, Prions, and Parkinson’s Disease. Cody McCullough & Sara Homsi BCM 465 April 19 th , 2010. Parkinson’s Disease. 1817: James Parkinson Progressive neurodegenerative disorder 1.5 million Americans 85% are over age 65 60,000 new cases / year! 9.

urian
Download Presentation

α -synuclein, Lewy Bodies, Prions, and Parkinson’s Disease

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. α-synuclein, Lewy Bodies, Prions, and Parkinson’s Disease Cody McCullough & Sara Homsi BCM 465 April 19th, 2010

  2. Parkinson’s Disease • 1817: James Parkinson • Progressive neurodegenerative disorder • 1.5 million Americans • 85% are over age 65 • 60,000 new cases / year!9 Dr. James Parkinson

  3. A Few Famous People with PD

  4. http://www.hipusa.com/webmd/images/health_and_medical_reference/brain_and_nervous_system/Parkinsons_Disease_Frequently_Asked_Questions.jpghttp://www.hipusa.com/webmd/images/health_and_medical_reference/brain_and_nervous_system/Parkinsons_Disease_Frequently_Asked_Questions.jpg

  5. Tyrosine hydroxylase Dopamine Tyrosine http://en.wikipedia.org/wiki/File:L-tyrosine-skeletal.png http://encefalus.com/wp-content/uploads/2008/09/dopamine.jpg

  6. http://www.oralchelationblog.com/wp-content/uploads/2008/08/parkinsonsdopamine.jpg

  7. What causes PD?

  8. Lewy Bodies • Abnormal aggregates of proteins that develop inside nerve cells • α-synuclein aggregates + ubiquitin¹ http://en.wikipedia.org/wiki/File:Lewy_Koerperchen.JPG

  9. What is α-synuclein? • Small protein: 14kDa • Encoded by SNCA gene • Highly conserved; expressed in brain¹,⁷ http://www.bio.purdue.edu/people/faculty/cramer/images/Alpha-Synuclein.jpg

  10. α-synuclein transmission Neuron 1 Synapse α-synuclein Neuron 2

  11. Lewy Body Formation Aggregation A30P E46K A53T Neuronal Cell Death ⁸, 9 Savitt, J.M., V.L. Dawson, and T.M. Dawson. 2006. Diagnosis and treatment of Parkinson’s disease: molecules to medicine. J. Clin. Invest. 116: 1744-1754.

  12. α-synuclein as a Prion? • An infectious agent made up of protein (PrPC) • α-helical conformation • β-sheet conformation  amyloid fibrils6 • Aggregation & transmission of the misfolded protein thought to be toxic 6

  13. Previous Findings • α-synuclein and its aggregates can be exocytosed from neuronal cells³ • α-synuclein and its aggregates can be endocytosed by neurons in culture⁴,⁵

  14. Desplats Paper • Demonstrates that nerve cells overexpressingα-synuclein can transmit the protein to healthy grafted neural stem cells in both in vitro and in vivo models² • Tests if α-synuclein pathology involves direct neuron-to-neuron transmission of α-synuclein aggregates via endocytosis • “There is much to suggest that α-synuclein behaves like a prion.” 6

  15. References • Cookson, M.R. 2005. The biochemistry of Parkinson’s disease. Annu. Rev. Biochem. 74: 29-52. • Desplats, P., Lee, H-J., Bae, E-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., and S-J. 2009. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein. PNAS 106: 13010-13015. • Lee, H-J., Patel, S., and S-J. Lee. 2005. Intravascular localization and exocytosis of α-synuclein and its aggregates. J Neurosci25: 6016-6024. • Lee, H-J., et al. 2008. Assembly-dependent endocytosis and clearance of extrancellularα-synuclein. Int J Biochem Cell Biol 40: 1835-1849. • Lee, H-J., Suk, J.E., Bae, E.J., and S-J. Lee. 2008. Clearance and deposition of extracellular α-synuclein aggregates in microglia. BiochemBiophys Res Commun372: 423-428. • Olanowa, C.W., and S.B. Prusiner. 2009. Is Parkinson’s disease a prion disorder? PNAS 106: 12571-12571. • Savitt, J.M., Dawson, V.L., and T.M. Dawson. 2006. Diagnosis and treatment of Parkinson’s disease: molecules to medicine. J. Clin. Invest. 116: 1744-1754. • Wood-Kaczmar, A., Gandhi, S., and N.W. Wood. 2006. Understanding the molecular causes of Parkinson’s disease. Trends Mol. Med. 12: 521-528. • Brown University, Deep Brain Stimulation: Parkinson's Disease

More Related