Showing papers by "Sandra M. Cardoso published in 2007"
TL;DR: It is demonstrated that functional mitochondria are required for cell death as a result of ER stress triggered by the PrP peptide, and further elucidate the molecular mechanisms involved in the neuronal loss that occurs in prion disorders.
Abstract: Prion disorders are progressive neurodegenerative diseases characterized by extensive neuronal loss and by the accumulation of the pathogenic form of prion protein, designated PrP(Sc). Recently, we have shown that PrP(106-126) induces endoplasmic reticulum (ER) stress, leading to mitochondrial cytochrome c release, caspase 3 activation and apoptotic death. In order to further clarify the role of mitochondria in ER stress-mediated apoptotic pathway triggered by the PrP peptide, we investigated the effects of PrP(106-126) on the Ntera2 human teratocarcinoma cell line that had been depleted of their mitochondrial DNA, termed NT2 rho0 cells, characterized by the absence of functional mitochondria, as well as on the parental NT2 rho+ cells. In this study, we show that PrP(106-126) induces ER stress in both cell lines, given that ER Ca2+ content is low, glucose-regulated protein 78 levels are increased and caspase 4 is activated. Furthermore, in parental NT2 rho+ cells, PrP(106-126)-activated caspase 9 and 3, induced poly (ADP-ribose) polymerase cleavage and increased the number of apoptotic cells. Dantrolene was shown to protect NT2 rho+ from PrP(106-126)-induced cell death, demonstrating the involvement of Ca2+ release through ER ryanodine receptors. However, in PrP(106-126)-treated NT2 rho0 cells, apoptosis was not able to proceed. These results demonstrate that functional mitochondria are required for cell death as a result of ER stress triggered by the PrP peptide, and further elucidate the molecular mechanisms involved in the neuronal loss that occurs in prion disorders.
57 citations
01 Jan 2007
TL;DR: This chapter resumes some of the findings that provide evidence for the role of mitochondria in neurodegeneration associated with Parkinson's disease and Huntington’s disease, two Neurodegenerative disorders that cause movement disturbances.
Abstract: Mitochondria play an important role as ATP producers through the activity of the citric acid cycle and oxidative phosphorylation, as regulators of intracellular calcium homeostasis, and producers of endogenous reactive oxygen species (ROS). Mitochondria also regulate cell death, marking the point of no return in necrosis and apoptosis. Many evidences have been raised implicating mitochondria defects as crucial mechanisms in the pathogenesis of several neurodegenerative diseases, as well as in aging. This chapter resumes some of the findings that provide evidence for the role of mitochondria in neurodegeneration associated with Parkinson’s disease (PD) and Huntington’s disease (HD), two neurodegenerative disorders that cause movement disturbances.
3 citations