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Purkinje‐cell degeneration in prion protein‐deficient mice is associated with a cerebellum‐specific Doppel protein species signature
Author(s) -
Al Bersaoui Roméo,
Robert Isabelle,
Lutz Yves,
Blanc Frédéric,
Sommermeyer-Leroux Ghislaine,
Shibaguchi Hirotomo,
Aunis Dominique,
Fuchs Jean-Paul
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.04.007
Subject(s) - prnp , neurotoxicity , cerebellum , cerebellar degeneration , purkinje cell , biology , neuroprotection , immunohistochemistry , antibody , prion protein , neuroscience , microbiology and biotechnology , pathology , immunology , medicine , toxicity , disease
PrP c (cellular prion protein) and Doppel are antagonizing proteins, respectively neuroprotective and neurotoxic. Evidence for Doppel neurotoxicity came from PrP c ‐deficient ( Prnp 0/0 ) mouse lines developing late onset Purkinje‐cell degeneration caused by Doppel overexpression in brain. To address the molecular underpinnings of this cell‐type specificity, we generated Doppel N‐terminal‐specific antibodies and started to examine the spatio‐temporal expression of Doppel protein species in Ngsk Prnp 0/0 brain. Although Doppel overexpression is ubiquitous, Western analyses of normal and deglycosylated protein extracts revealed cerebellar patterns distinct from the rest of the brain, supporting the idea that neurotoxicity might be linked to a particular Doppel species pattern. Furthermore, our newly raised antibodies allowed the first Doppel immunohistochemical analyses in brain, showing a distribution in Prnp 0/0 cerebellum similar to PrP c in wild type.