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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, Carmina C; Silbern, Ivan; Caldi Gomes, Lucas; Wartmann, Hannes; Dambeck, Vivian; Fanz, Jonas; Neuenroth, Lisa; Bähr, Mathias; Outeiro, Tiago F; Bonn, Stefan; Stadelmann-Nessler, Christine; Rizzoli, Silvio O; Lenz, Christof; Urlaub, Henning; Lingor, Paul.
Afiliación
  • Warth Perez Arias CC; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
  • Silbern I; Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany.
  • Caldi Gomes L; Collaborative Research Center 1286 "Quantitative Synaptology", University of Göttingen, Göttingen, Germany.
  • Wartmann H; Collaborative Research Center 1286 "Quantitative Synaptology", University of Göttingen, Göttingen, Germany.
  • Dambeck V; Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
  • Fanz J; Bioanalytics Group, Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Neuenroth L; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
  • Bähr M; Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany.
  • Outeiro TF; Clinical Department of Neurology, School of Medicine, rechts der Isar Hospital, Technical University of Munich, Munich, Germany.
  • Bonn S; Institute for Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Stadelmann-Nessler C; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
  • Rizzoli SO; Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany.
  • Lenz C; Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
  • Urlaub H; Göttingen Campus Institute for Dynamics of Biological Networks (CIDBN), University of Göttingen, Göttingen, Germany.
  • Lingor P; Bioanalytics Group, Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
J Neurochem ; 166(5): 862-874, 2023 09.
Article en En | MEDLINE | ID: mdl-37515330
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedad de Alzheimer Tipo de estudio: Risk_factors_studies Límite: Humans / Middle aged Idioma: En Revista: J Neurochem Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Enfermedad de Alzheimer Tipo de estudio: Risk_factors_studies Límite: Humans / Middle aged Idioma: En Revista: J Neurochem Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido