Wyniki wyszukiwania

1

Genetic aspects of Alzheimer's disease

100%

Zekanowski C., Religa D., Graff C., Filipek S., Kuznicki J.

Acta Neurobiologiae Experimentalis

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2004

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tom 64

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nr 1

2

Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

84%

Adamczyk A., Czapski G. A., Jesko H., Strosznajder R. P.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 2

5-13

Amyloid beta peptide (Aß) and non-Aß component of Alzheimer’s disease amyloid (NAC) are involved in pathomechanism of Alzheimer's Disease (AD) and are deposited in the AD brain in the form of senile plaques. However, the mechanism of their neurotoxicity is not fully understood. In this study the sequence of events involved in NAC and Aß peptides evoked toxicity was investigated in brain slices, synaptosomes and in subcellular fractions. Radio-, immunochemical, spectrophotometrical methods and DNA electrophoresis were used in this study. Our data indicated that Aß 1-40 (25 µM) and NAC (10 µM) peptides induced liberation of free radicals and massive DNA damage that lead to activation of DNA bound enzyme poly(ADP-ribose) polymerase-1 (PARP-1). In consequence of these processes apoptosis-inducing factor (AIF) was released from mitochondria and was translocated to nucleus. The inhibitor of PARP, 3-aminobenzamide significantly decreased AIF release from mitochondria and its translocation. Both peptides under the investigated conditions had no effect on caspase-3 activity. Our data indicated that Aß and NAC peptides stimulate AIF-dependent apoptotic pathway that seems to be caspase independent process. The inhibition of PARP-1 may protect the brain against Aß and NAC toxicity.

3

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress

84%

Strosznajder R. P., Jesko H., Banasik M., Tanaka S.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

215-221

Our previous data indicate that ischemia and amyloid beta peptide (Abeta) cause an oxidative damage to macromolecules. In the present study we investigated the role of p53 protein in cell survival and death after administration of Abeta. The experiments were carried out on pheochromocytoma cells (PC-12) and cortical primary neurons in culture. The cortical neurons were exposed (48 h, 10 µM) to the action of a short Abeta25-35 neurotoxic fragment and the involvement of p53 was evaluated after addition of the p53 inhibitor pifithrin-alpha. Changes in cell morphology were evaluated by 4', 6-diamidino-2-phenylindole staining and the concentration-dependent effect of pifithrin-alpha on cells viability was determined. Additionally, we studied the effect of pifithrin-alpha on neuronal survival in vivo after a 5-min global brain ischemia followed by 7 days' reperfusion in gerbils. We found that Abeta enhanced apoptotic cell death in cortical primary neurons. Pifithrin-alpha, at a 10 µM final concentration, protected the neuronal cells from the apoptotic death. However, at concentrations of 0.1 and 1 mM, the p53 inhibitor decreased PC-12 cells' viability in a dose-dependent manner. In in vivo experiments we did not observe any neuroprotection by pifithrin-alpha in the CA1 hippocampal layer, which suggests that its effects strongly depend on the duration and type of an ischemic insult. Our data indicate that pifithrin-alpha affects neuronal cells in a dual manner. It has a protective effect at a low concentration, but becomes neurotoxic at higher concentrations.

4

Alzheimer’s amyloid beta peptides disturb circadian oscillations of intracellular calcium concentration

84%

Kazmierczak A., Schmitt K., Grimm A., Strosznajder J. B., Eckert A.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

It is postulated that disturbances in calcium homeostasis play an important role in pathogenesis of Alzheimer’s disease (AD). Changes of neuronal calcium concentration are responsible for the oxidative stress as well as altered metabolism and production of amyloid-beta peptides (Aβ). Aβ may further exacerbate calcium dysregulation, causing synaptic dysfunction, neurodegeneration and cognitive impairment. Recent data indicate that AD is associated with disturbances of circadian rhythm in the patients. However, till now nothing is known about the molecular mechanisms involved in AD-related circadian clock alterations. In our study we investigated the effect of Aβ peptides on the rhythmic oscillation of cytosolic and mitochondrial calcium levels. To investigate molecular clock mechanisms, the studies we carried out in human primary skin fibroblasts, a previously established experimental model. Our data showed circadian rhythm of calcium ions concentration in cytosol and mitochondria. Moreover we observed circadian oscillation of ROS formation and redox potential. Treatment with Aβ fibrils at the concentration of 0.5 µM disturbed cytosolic calcium oscillations and mitochondrial redox state. Studying mechanisms involved in this phenomenon indicated that Aβ did not affect ER calcium stores, but induced changes of calcium influx mediated by purinergic P2X7 receptor. The specific antagonist of P2X7 receptor Brillant Blue G abolished negative impact of Aβ and restored calcium circadian rhythm. Summarizing, our results indicate that Aβ may play a significant role in disturbances of circadian calcium oscillation, suggesting the importance of this phenomenon in ADrelated changes in biological clock. Supported by grants from Sciex 10. 258 to A.K. as well as Swiss National foundation (SNF No 310030_122572) and Synapsis Foundation to A.E.

5

Therapeutic strategies for Alzheimer's disease based on new molecular mechanisms

84%

Religa D., Winblad B.

Acta Neurobiologiae Experimentalis

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2003

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tom 63

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nr 4

6

The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain

67%

Varnum M. M., Ikezu T.

Archivum Immunologiae et Therapiae Experimentalis

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2012

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tom 60

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nr 4

7

Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases

67%

Greig N. H., Giordano T., Zhu X., Yu Q., Perry T. A., Holloway H. W., Brossi A., Rogers J. T., Sambamurti K., Lahiri D. K.

Acta Neurobiologiae Experimentalis

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2004

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tom 64

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nr 1

Ograniczanie wyników

Genetic aspects of Alzheimer's disease

Non-Abeta component of Alzheimer's disease amyloid and amyloid beta peptides evoked poly(ADP-ribose) polymerase-dependent release of apoptosis-inducing factor from rat brain mitochondria

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress

Alzheimer’s amyloid beta peptides disturb circadian oscillations of intracellular calcium concentration

Therapeutic strategies for Alzheimer's disease based on new molecular mechanisms

The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer’s disease brain

Thalidomide-based TNF-alpha inhibitors for neurodegenerative diseases