Gama-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 co-localization of gama-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. Gamma enolase intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque and was proved to be neuroprotective against Aß toxicity.
COBISS.SI-ID: 3441265
Gama-enolase exerts a protective effect against amyloid-ß-peptide (Aß)-induced neurotoxicity in PC12 cells. Aß-induced toxicity was abolished in the presence of the active C-terminal peptide of gamma-enolase, which caused downregulation of the pro-apoptotic protein Bax and upregulation of the anti-apoptotic protein Bcl-2, as well as reduced caspase-3 activation. Exposure to Aß increased surface expression of p75 neurotrophin receptor (p75NTR), and the pretreatment with gamma enolase peptide suppressed the activation of mitogen-activated protein kinases p38 and Jun-N-terminal kinase, which are p75NTR downstream effectors in apoptotic signaling. Gamma enolase also colocalized with p75NTR. Our results indicate the possible use of gama enolase C-terminal peptide for treating or preventing Alzheimer's disease.
COBISS.SI-ID: 3492209
Here we present profilin 1, a known tumor suppressor, as a target for cathepsin X in prostate cancer PC-3 cells. Profilin 1 co-localizes strongly with cathepsin X intracellularly in the perinuclear area as well as at the plasma membrane. Selective cleavage of C-terminal amino acids was demonstrated on a synthetic peptide and on recombinant profilin 1. Intact profilin 1 binds its poly-L-proline ligand clathrin significantly better than it does the truncated one, as shown using cathepsin X specific inhibitor AMS-36 and immunoprecipitation of the profilin 1/clathrin complex. Moreover, the polymerization of actin, which depends also on the binding of poly-L-proline ligands to profilin 1, was promoted by AMS-36 treatment of cells and by siRNA cathepsin X silencing.
COBISS.SI-ID: 3375217