Abstract
Ubiquitin-proteasome system (UPS) represents important intracellular system controlling protein quality and intracellular signalling. Overload or dysfunction of UPS leads to proteasome stress that is implicated in mechanisms of neurodegeneration associated with neurodegenerative diseases, e. g. Parkinson and Alzheimer disease. Proteasome stress is also considered as the main cause of delayed neuronal death observed after transient global brain ischemia. Despite significant progress made to date, the exact mechanism and selectivity of cell death induced by proteasome stress after global brain ischemia is still not completely understood. The aim of our work was to study effect of proteasome stress on cell viability, stress response as well as on mechanism of death of neuroblastoma SH-SY5Y and glioblastoma T98G cells. Proteasome stress was induced by treatment of cells with bortezomib, inhibitor of proteasome 26S complex. Neuroblastoma cells were more sensitive to bortezomib than glioblastoma cells and death of neuroblastoma cells occurred significantly faster than death of glioblastoma cells. With respect to cellular response, treatment of both SH-SY5Y and T98G cells with bortezomib was associated with accumulation of polyubiquitinylated protein aggregates and increased expression of HSP70. With respect to cell death mechanism, we have documented bortezomib-induced release of cytochrome c from mitochondria and activation of caspase 3 in SH-SY5Y cells. In T98G cells, bortezomib induced activation of caspase 4 but not caspase 3 and did not induce release of cytochrome c from mitochondria. Our results indicate that proteasome stress affects neural cells in different way but does not answer the question about selectivity and delay of cell after global brain ischemia.
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
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
