Complement and coagulation cascades are potentially involved in dopaminergic neurodegeneration in α-synuclein-based mouse models of Parkinson’s disease

Shi Xun Ma, Donghoon Kim, Yulan Xiong, Seung Hwan Kwon, Saurav Brahmachari, Sangjune Kim, Tae In Kam, Raja Sekhar Nirujogi, Sang Ho Kwon, Valina L. Dawson, Ted M. Dawson, Akhilesh Pandey, Chan Hyun Na, Han Seok Ko

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that results in motor dysfunction and eventually, cognitive impairment. α-Synuclein protein has been known to be the most culprit protein, but the underlying pathological mechanism still remains to be elucidated. As an effort to clarify the pathogenesis mechanism by α-synuclein, various PD mouse models with α-synuclein overexpression have been developed. However, the systemic analysis of protein abundance change by the overexpressed α-synuclein in the whole proteome level has been still lacking. To address this issue, we established two sophisticated mouse models of PD by injecting α-synuclein preformed fibrils (PFF) or by inducing overexpression of human A53T α-synuclein to discover overlapping pathways, which could be altered in the two different types of PD mouse model. For more accurate quantification of mouse brain proteome, stable isotope labeling with amino acid in mammal-based quantification was implemented. As a result, we have successfully identified a total of 8,355 proteins from both of the mouse models; ∼6,800 and ∼7,200 proteins from α-synuclein PFF injected mice and human A53T α-synuclein transgenic mice, respectively. From the pathway analysis of the differentially expressed proteins in common, the complement and coagulation cascade pathway were determined as the most enriched ones. This is the first study that highlights the significance of the complement and coagulation pathway in the pathogenesis of PD through proteome analyses with two sophisticated mouse models of PD.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jan 13 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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