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
Cysteine protease inhibitors macrocypins, isolated from the parasol mushroom, and later prepared as recombinant proteins, inhibited the growth of Colorado potato beetle larve, presumably by inhibiting gut cysteine proteases. These results provide their potential applicability in pests control.
COBISS.SI-ID: 27291431
We present here the structure-based design and synthesis of new cathepsin B inhibitors using the cocrystal structure of 5-nitro-8-hydroxyquinoline in the cathepsin B active site. A focused library of over 50 compounds was prepared by modifying positions 5, 7,and 8 of the parent compound nitroxoline. The kinetic parameters and modes of inhibition were characterized, and the selectivities of the most promising inhibitors were determined. The best performing inhibitor 17 was effective in cell-based in vitro models of tumor invasion, where it significantly abrogated invasion of MCF-10A neoT cells.
COBISS.SI-ID: 3370865
The cytoskeletal protein talin, an actin- and beta-integrin tail-binding protein,plays an important role in cell migration by promoting integrin activation and focal adhesion formation. Here, we show that talin is a substrate for cathepsin H (CtsH), a lysosomal cysteine protease with a strong aminopeptidase activity. The attenuation of CtsH aminopeptidase activity by a specific inhibitor or siRNA-mediated silencing significantly reduced the migration of PC-3 cells on fibronectin and invasion through Matrigel. We propose that CtsH-mediated processing of talin might promote cancer cell progression by affecting integrin activation and adhesion strength.
COBISS.SI-ID: 3390321
We report that transgenic mice overexpressing wild-type human FUS develop an aggressive phenotype amyotrophic lateral sclerosis (ALS). Surviving motor neurons in the spinal cord had greatly increased cytoplasmic expression of FUS, with globular and skein-like FUS-positive and ubiquitin-negative inclusions associated with astroglial and microglial reactivity.These findings suggest that overexpression of wild-type FUS in vulnerable neurons may be one of the root causes of disease.
COBISS.SI-ID: 26073127