Accession Number:

ADA606023

Title:

Interaction of Synuclein and Inflammation in Dopaminergic Neurodegeneration

Descriptive Note:

Final rept. 30 Jun 2008-31 Mar 2014

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

• Przedborski, Serge
• Jackson-Lewis, Vernice

Report Date:

2014-06-01

Pagination or Media Count:

31.0

Abstract:

Inflammation is now considered a hallmark of Parkinson s disease PD. As such, it is necessary to understand how this inflammation arises and how it may contribute to the propagation of PD. We and others believe that synuclein may be the cause of this inflammatory response due to its release into the extracellular space. Here, we used immortalized N9 cells and NCD36 deficient microglial cells in our studies on synuclein-induced inflammation. Furthermore, we clarified some of our results in paraffin-embedded substantia nigra pars compacta SNpc. Using the aforementioned cells and several different cell culture experiments with wild-type WT and mutated synuclein, we found that both types of synuclein increase microglial adhesion and decrease microglial migration. Several antibodies inteferred with the synuclein effects by blocking the synuclein-induced decrease in migratory behavior and increase in adhesive behavior of the microglia. Using WT fluorescent synuclein-coated nanobeads, we saw that synuclein not only stuck to the surface of the microglia, but was also internalized by the microglia. We believe that this occurred through CD36 and CD11b. Since we saw that our results were not 100, we believe that other scavenger receptors and integrins are involved. Immumostaining of the SNpc showed a robust staining for CD36. We are now working on a two color immunostaining for CD36 localization in which cells. From these studies, we conclude that CD36 and CD11b are major players in the inflammatory response induced by the synucleins.

Descriptors:

• *CELLS(BIOLOGY)
• *INFLAMMATION
• *PARKINSONS DISEASE
• DEGENERATION(PHYSIOLOGY)
• DOPAMINE
• INTEGRINS
• INTERACTIONS

Subject Categories:

• Biology
• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE