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 Neurochemistry166(5) pp. 862​-874​.​ DOI: https://doi.org/10.1111/jnc.15924 

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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 
External URL
https://mbexc.uni-goettingen.de/literature/publications/736
https://sfb1286.uni-goettingen.de/literature/publications/213
ISSN
0022-3042
eISSN
1471-4159
Language
English
Sponsor
Volkswagen Foundation https://doi.org/10.13039/501100001663

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