Bioenergetic and Proteomic Analysis of Striatal Synaptosomes from PINK1/Parkin Double Knockout Rats
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College, Institute, or Department
MD/PhD Scholars Program
Dr. Kelly Stauch
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.
Parkinson's Disease, Proteomics, PINK1/Parkin, Synaptosomes, Bioenergetics
Shomali, Jacob; Totusek, Steven; and Stauch, Kelly, "Bioenergetic and Proteomic Analysis of Striatal Synaptosomes from PINK1/Parkin Double Knockout Rats" (2020). Posters: 2020 Summer Undergraduate Research Program. 25.