Bioenergetic and Proteomic Analysis of Striatal Synaptosomes from PINK1/Parkin Double Knockout Rats

Title

Bioenergetic and Proteomic Analysis of Striatal Synaptosomes from PINK1/Parkin Double Knockout Rats

Files

Download Jacob Shomali Original Presentation File (986 KB)

Loading...

Media is loading
 

Publication Date

Summer 8-6-2020

College, Institute, or Department

MD/PhD Scholars Program

Faculty Mentor

Dr. Kelly Stauch

Research Mentor

Joseph George

Document Type

Poster

Abstract

Parkinson’s disease (PD) patients exhibit dopaminergic (DA) neuron degeneration in the substantia nigra pars compacta (SNpc) and loss of associated terminals in the striatum, which results in motor deficits. Loss-of-function gene mutations in PINK1 and Parkin (proteins relevant to mitochondrial quality control) have been identified in hereditary PD patients and show promise for PD animal models. Without a reproducible PD mammalian model, previous studies have failed to observe the mechanisms of progressive neurodegeneration. Therefore, we created and characterized a PINK1/Parkin double knockout (DKO) rat that reproducibly (100% of males) exhibits PD-relevant pathology, including striatal nerve terminal bioenergetic deficits prior to significant motor impairments and DA neuron loss in the SNpc. With mass spectrometry-based proteomics, we identified the differentially expressed proteins in the striatal synaptosomes (a portion of which originate from the SNpc) of DKO rats. Our results indicate decreased expression of mitochondrial and neurotransmitter release proteins. Thus, the DKO rats exhibit deficient neuronal communication.

Keywords

Parkinson's Disease, Proteomics, PINK1/Parkin, Synaptosomes, Bioenergetics

Bioenergetic and Proteomic Analysis of Striatal Synaptosomes from PINK1/Parkin Double Knockout Rats

Share

COinS