Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto-axonal target in late-stage Parkinson's disease

Carmina C. Warth Perez Arias, Ivan Silbern, Lucas Caldi Gomes, Hannes Wartmann, Vivian Dambeck, Jonas Fanz, Lisa Neuenroth, Mathias Bähr, Tiago F. Outeiro, Stefan Bonn, Christine Stadelmann-Nessler, Silvio O. Rizzoli, Christof Lenz, Henning Urlaub, Paul Lingor

Research output: Contribution to journalArticlepeer-review

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. (Figure presented.).

Original languageEnglish
Pages (from-to)862-874
Number of pages13
JournalJournal of Neurochemistry
Volume166
Issue number5
DOIs
StatePublished - Sep 2023
Externally publishedYes

Keywords

  • Parkinson's disease
  • neurodegeneration
  • proteomics
  • synaptic dysfunction

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