Summaryc-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 c-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein.In situ hybridization of c-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 c-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 c-enolase in microglial cells in response to amyloid-b peptide (Ab) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with c-enolase proved to be neuroprotective against Ab toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of c-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-b-related neurodegeneration.

Synaptotagmins (Syts) are transmembrane proteins involved in the regulation of membrane trafficking. Here, we summarize literature data that provide growing evidence that several Syts are involved in the pathophysiological mechanisms of temporal lobe epilepsy and Parkinson's disease, as well as few reports related to brain ischemia and Alzheimer's disease (AD). We also report new data from our laboratories, showing changes of the expression of several Syts in Tg2576 mouse model of AD that may be related to neuroinflammation surrounding the b-amyloid plaques. Furthermore, we demonstrate N-methyl-D-aspartate receptor-mediated upregulation of Syt 4 mRNA in a model of excitotoxic striatal lesion induced by unilateral striatal injection of quinolinic acid, associating the upregulation of Syt 4 with mechanisms of excitotoxicity. We propose that phamacological manipulation of Syt expression in animal models of neurodegeneration should be further explored, as it may help to clarify the role of individual Syt isoforms in the regulation of membrane trafficking in neurodegeneration.

No abstract

Varroa destructor is one of the most common parasites of honey bee colonies and is considered as a possible co-factor for honey bee decline. At the same time, the use of pesticides in intensive agriculture is still the most effective method of pest control. There is limited information about the effects of pesticide exposure on parasitized honey bees. Larval ingestion of certain pesticides could have effects on honey bee immune defense mechanisms, development and metabolic pathways. Europe and America face the disturbing phenomenon of the disappearance of honey bee colonies, termed Colony Collapse Disorder (CCD). One reason discussed is the possible suppression of honey bee immune system as a consequence of prolonged exposure to chemicals. In this study, the effects of the neonicotinoid thiamethoxam on honey bee, Apis mellifera carnica, pupae infested with Varroa destructor mites were analyzed at the molecular level. Varroa-infested and non-infested honey bee colonies received protein cakes with or without thiamethoxam. Nurse bees used these cakes as a feed for developing larvae. Samples of white-eyed and brown-eyed pupae were collected. Expression of 17 immune-related genes was analyzed by real-time PCR. Relative gene expression in samples exposed only to Varroa or to thiamethoxam or simultaneously to both Varroa and thiamethoxam was compared. The impact from the consumption of thiamethoxam during the larval stage on honey bee immune related gene expression in Varroainfested white-eyed pupae was reflected as down-regulation of spaetzle, AMPs abaecin and defensin-1 and up-regulation of lysozyme-2. In brown-eyed pupae up-regulation of PPOact, spaetzle, hopscotch and basket genes was detected. Moreover, we observed a major difference in immune response to Varroa infestation between white-eyed pupae and brown-eyed pupae. The majority of tested immune-related genes were upregulated only in brown-eyed pupae, while in white-eyed pupae they were downregulated.

No abstract

No abstract

Neuroinflammation is an important factor in the pathogenesis of neurodegenerative diseases. Microglia-derived lysosomal cathepsins have been increasingly recognized as important inflammatory mediators that trigger signaling pathways that aggravate neuroinflammation. In vitro, a contribution to neuroinflammation processes has been shown for cathepsin X: however, the expression patterns and functional role of cathepsin X in neuroinflammatory brain pathology remain elusive. In this study we analyzed the expression, activity, regional distribution and cellular localization of cathepsin X in the rat brain with neuroinflammation-induced neurodegeneration. The unilateral injection of lipopolysaccharide (LPS) induced a strong upregulation of cathepsin X expression and its activity in the ipsilateral striatum. In addition to the striatum, cathepsin X overexpression was detected in other brain areas such as the cerebral cortex, corpus callosum, subventricular zone and external globus pallidus, whereas the upregulation was mainly restricted to activated microglia and reactive astrocytes. Continuous administration of the cathepsin X inhibitor AMS36 indicated protective effects against LPS-induced striatal degeneration, as seen by the attenuated LPS-mediated dilation of the lateral ventricles and partial decreased extent of striatal lesion. Taken together, our results indicate that cathepsin X plays a role as a pathogenic factor in neuroinflammation-induced neurodegeneration and represents a potential therapeutic target for neurodegenerative diseases associated with neuroinflammation.

No abstract