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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. 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. (Figure presented.).
Author(s): Warth Perez Arias CC, Silbern I, Caldi Gomes L, Wartmann H, Dambeck V, Fanz J, Neuenroth L, Bahr M, Outeiro TF, Bonn S, Stadelmann-Nessler C, Rizzoli SO, Lenz C, Urlaub H, Lingor P
Publication type: Article
Publication status: Published
Journal: Journal of Neurochemistry
Year: 2023
Volume: 166
Issue: 5
Pages: 862-874
Print publication date: 01/09/2023
Online publication date: 28/07/2023
Acceptance date: 17/07/2023
Date deposited: 31/08/2023
ISSN (print): 0022-3042
ISSN (electronic): 1471-4159
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1111/jnc.15924
DOI: 10.1111/jnc.15924
Data Access Statement: The proteomics dataset was deposited in the Proteomics Identifications Database (PRIDE), following applicable guidelines. Data are available via ProteomeXchange (https://www.proteomexchange.org/) with the identifiers PXD033990 (WTL data) and PXD033951 (SF data).
PubMed id: 37515330
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