The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Dement.
Sec. Cellular and Molecular Mechanisms of Dementia
Volume 3 - 2024 |
doi: 10.3389/frdem.2024.1477986
Quantitative proteomic analysis using a mouse model of Lewy Body Dementia (LBD) induced by α-synuclein preformed fibrils injection
Provisionally accepted- 1 Institute for Cell Engineering, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States
- 2 The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- 3 Department of Biomedical Engineering, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States
- 4 Department of Neurology and Neurosurgery, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States
The aggregation of α-synuclein in the nervous system leads to a class of neurodegenerative disorders termed α-synucleinopathies. A form of primary degenerative dementia called Lewy body dementia (LBD) often develops when these aggregations develop into intracellular inclusions called Lewy bodies (LB) and Lewy neurites (LN). Although high frequency of LBD are the leading cause of dementia after Alzheimer's disease (AD), limited information has been discovered about its pathological pathway or diagnostic criteria. In this report, we attempt to address such shortcomings via utilizing a proteomic approach to identify the proteome changes following intrastriatal injection of α-synuclein pre-formed fibril (α-syn PFF). Using mass spectrometry, we have identified a total of 179 proteins that were either up-or down-regulated at different time points, with the four proteins -TPP3, RAB10, CAMK2A, and DYNLL1, displaying the most significant changes throughout the timeframe. Through further examining the modulated proteins with network-based enrichment analyses, we have found that 1) the most significantly associated neurodegenerative pathways were Parkinson's (pV = 3.0e-16) and Huntington's (pV = 1.9e-15) disease, and 2) the majority of molecular functions specific to the pathology only appeared at later time points. While these results do not expose a conclusive biomarker for LBD, they suggest a framework that is potentially applicable to diagnose and differentiate LBD pathology from other forms of dementia by focusing on the cortical proteome changes which occur in a later time span.
Keywords: Parkinson's disease with dementia, Lewy body dementia (LBD), Quantitative Proteomics, TMT-isobaric mass technique, synucleinopathy models
Received: 08 Aug 2024; Accepted: 14 Oct 2024.
Copyright: © 2024 Akkentli, Jang, Choi, Min, Park, Jo, Kim, Mendpara, Bains, Yoo, Xu, Na and Kang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sung Ung Kang, Institute for Cell Engineering, School of Medicine, Johns Hopkins Medicine, Baltimore, MD 21205-1832, Maryland, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.