Abstract
Development of the nervous system and its structural remodelling in the adult relies on molecules mediating the structural plasticity of neurons, e specially those involved in cell adhesion, cytoskeletal dynamics or synapse formation. Neural cell adhesion molecule (NCAM) is a membrane-associated glycoprotein that can be modified by glycosylation with polysialic acid (PSA), attenuating NCAM-mediated cell interactions, thereby promoting structural plasticity [1]. It has been demonstrated that in conditions of neuroinflammation, NCAM can be cleaved extracellularly by metalloproteinases and other proteolytical enzymes. Prolyl endopeptidase (PREP) is a cytosolic serine protease, and alterations in PREP expression and activity have been associated with neuronal death and neuroinflammation [2]. Since the precise mechanisms and possible partners of PREP in neuroinflammation remain unclear, the aim of this study was to determine whether increased secretion and activation of PREP could impair NCAM expression and its polysialylation. SH-SY5H cell line overexpressing (o/e) PREP was used as an in vitro model for increased PREP expression and extracellular release. When measuring expression levels of NCAM and PSA-NCAM we found remarkable loss in PSA-NCAM and disrupted expression patterns of NCAM compared to wild-type cells. As matrix metalloproteinase 9 (MMP-9) has been indicated in processes regulating shedding of PSA-NCAM, MMP-9 expression level was measured. An increase in the level of the active form of MMP-9 was found, which was counteracted by a specific inhibitor of PREP, KYP-2047. As demonstrated, PREP might have an important role in processes involved in NCAM degradation and polysialylation, thereby inducing progression of pathologies associated with altered neuroplasticity.
Highlights
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia
The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression
No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression
Summary
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors
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