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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

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.).

Publication metadata

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.


DOI: 10.1111/jnc.15924

PubMed id: 37515330


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Funder referenceFunder name
Göttingen Graduate Center for Neurosciences, Biophysics, and Molecular Biosciences (GGNB)
Ministry for Science and Education of Lower Saxony
National Council of Science and Technology (CONACYT), Mexico's Federal Government (CCWPA)
Munich Cluster for Systems Neurology (SyNergy)
SFB 1286 "Quantitative Synaptology"
Volkswagen Foundation