title: Neuroprotective role of γ-enolase in microglia in a mouse model of Alzheimer's disease is regulated by cathepsin X.
abstract: γ-Enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C-terminal end of the molecule. We have investigated the expression and colocalization of γ-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of γ-enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C-terminally cleaved form of γ-enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of γ-enolase in microglial cells in response to amyloid-β peptide (Aβ) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with γ-enolase proved to be neuroprotective against Aβ toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of γ-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-β-related neurodegeneration.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, Ljubljana, 1000, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Hafner
authors.forename: Gordana
authors.initials: G
authors.lastname: Glavan
authors.forename: Nataša
authors.initials: N
authors.lastname: Obermajer
authors.forename: Marko
authors.initials: M
authors.lastname: Živin
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schliebs
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D056663:Cathepsin Z / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D016501:Neurites / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D056663:Cathepsin Z; C534184:Ctsz protein, mouse; D010751:Phosphopyruvate Hydratase
keywords: Alzheimer's disease; amyloid-β; cathepsin X; microglia; neuroprotection; γ-Enolase