title: Comparative proteomics in neurodegenerative and non-neurodegenerative diseases suggest nodal point proteins in regulatory networking.
abstract: Neurodegenerative disorders (ND) encompass clinically and genetically heterogeneous diseases with considerable overlap of their clinical, neuropathological and molecular phenotype. Various causes of neurodegeneration in disease may affect eventually the same proteins within protein networks. To identify common changes in ND, we compared brain protein changes detected by 2-D electrophoresis in four mouse models for ND: (i) Parkinson's disease, (ii) Huntington's disease, (iii) prion disease Scrapie, and (iv) a model for impaired synaptic transmission. To determine specificity of these changes for ND, we extended the scope of our investigation to three neurological conditions that do not result in neurodegeneration (non-ND). We detected 12 to 216 consistent qualitative or quantitative protein changes in individual ND and non-ND models when compared to controls. Up to 36% of these proteins were found to be altered in multiple disease states (at least three) and were therefore termed nodal point proteins. Alterations in alpha B-Crystallin and splicing factor 3b (subunit 4) occurred in at least three ND but not in non-ND. In contrast, alterations in peroxiredoxin 1 and 3, astrocytic phosphoprotein PEA15, complexin 2 and aminoacylase 1 were common to both ND and non-ND. Finally, we investigated the expression pattern of the nodal point proteins in three inbred mouse strains and found different protein abundance (expression polymorphisms) in all cases. Nodal point proteins showing expression polymorphisms may be candidate proteins for disease associated modifiers.
authors.affiliation: Institute of Human Genetics, Charité, University Medicine Berlin, Augustenbuger Platz 1, 13353 Berlin, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Zabel
authors.forename: Dijana
authors.initials: D
authors.lastname: Sagi
authors.forename: Angela M
authors.initials: AM
authors.lastname: Kaindl
authors.forename: Nicole
authors.initials: N
authors.lastname: Steireif
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kläre
authors.forename: Lei
authors.initials: L
authors.lastname: Mao
authors.forename: Hartmut
authors.initials: H
authors.lastname: Peters
authors.forename: Maik A
authors.initials: MA
authors.lastname: Wacker
authors.forename: Ralf
authors.initials: R
authors.lastname: Kleene
authors.forename: Joachim
authors.initials: J
authors.lastname: Klose
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D001927:Brain Diseases / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D040901:Proteomics
chemical_list: D009419:Nerve Tissue Proteins