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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., Gomes, L. C., Wartmann, H., Dambeck, V., Fanz, J., et al. (2023). Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto-axonal target in late-stage Parkinson's disease. Journal of Neurochemistry, 166(5), 862-874. doi:10.1111/jnc.15924.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000D-BE9E-C Version Permalink: https://hdl.handle.net/21.11116/0000-000D-BEA1-7
Genre: Journal Article

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Journal of Neurochemistry - 2023 - Warth Perez Arias.pdf (Publisher version), 5MB
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Warth Perez Arias, Carmina C. , Author
Silbern, Ivan, Author
Gomes, Lucas Caldi, Author
Wartmann, Hannes, Author
Dambeck, Vivian, Author
Fanz, Jonas, Author
Neuenroth, Lisa, Author
Baehr, Mathias, Author
Outeiro, Tiago Fleming1, Author           
Bonn, Stefan2, Author           
Stadelmann-Nessler, Christine, Author
Rizzoli, Silvio O., Author
Lenz, Christof2, Author           
Urlaub, Henning2, Author           
Lingor, Paul, Author
Affiliations:
1Guest Group Experimental Neurodegeneration, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3505608              
2Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, Göttingen, DE, ou_3350290              

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 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.

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Language(s): eng - English
 Dates: 2023-07-282023-09
 Publication Status: Issued
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1111/jnc.15924
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Project name : This study was supported by the SFB 1286 “Quantitative Synaptology” (PL, IS, CL, TFO, SB, SOR, HU) and funds from the Scholarship program “Beca al extranjero,” from the National Council of Science and Technology (CONACYT), Mexico's Federal Government (CCWPA). PL was further supported by the Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. LCG received Bridging Funds from the Göttingen Graduate Center for Neurosciences, Biophysics, and Molecular Biosciences (GGNB). JF is the member of the CIDBN which is funded by the Ministry for Science and Education of Lower Saxony and the Volkswagen Foundation through the program “Niedersächsisches Vorab”.
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Title: Journal of Neurochemistry
  Other : J. Neurochem.
Source Genre: Journal
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Publ. Info: Hoboken, New Jersey, USA : Wiley
Pages: - Volume / Issue: 166 (5) Sequence Number: - Start / End Page: 862 - 874 Identifier: ISSN: 0022-3042
CoNE: https://pure.mpg.de/cone/journals/resource/954925416956_1