Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 ( NPTX1 ) as synapto‐axonal target in late‐stage Parkinson's disease
2023 | journal article. A publication with affiliation to the University of Göttingen.
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Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 ( NPTX1 ) as synapto‐axonal target in late‐stage Parkinson's disease
Warth Perez Arias, C. C.; Silbern, I.; Caldi Gomes, L.; Wartmann, H.; Dambeck, V.; Fanz, J. & Neuenroth, L. et al. (2023)
Journal of Neurochemistry, 166(5) pp. 862-874. DOI: https://doi.org/10.1111/jnc.15924
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Details
- Authors
- Warth Perez Arias, Carmina C.; Silbern, Ivan; Caldi Gomes, Lucas; Wartmann, Hannes; Dambeck, Vivian; Fanz, Jonas; Neuenroth, Lisa; Bähr, Mathias; Outeiro, Tiago F.; Bonn, Stefan; Lingor, Paul
- Abstract
- Abstract Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. While symptomatic treatment is available for motor symptoms of PD, non‐motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD‐associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post‐mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late‐stage PD and represents a putative target for novel therapeutic strategies. image
- Issue Date
- 2023
- Journal
- Journal of Neurochemistry
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1286: Quantitative Synaptologie
SFB 1286 | A03: Dynamische Analyse der Remodellierung der extrazellulären Matrix (ECM) als Mechanismus der Synapsenorganisation und Plastizität - Working Group
- RG Bähr (Neurobiological Research Laboratory)
RG Outeiro (Experimental Neurodegeneration)
RG Rizzoli (Quantitative Synaptology in Space and Time)
RG Stadelmann-Nessler
RG Urlaub (Bioanalytische Massenspektrometrie)
RG Bonn - ISSN
- 0022-3042
- eISSN
- 1471-4159
- Language
- English
- Sponsor
- Volkswagen Foundation https://doi.org/10.13039/501100001663