Alzheimer Disease: Hugyecz M

Pákáski M, Hugyecz M, Sántha P, Jancsó G, Bjelik A, Domokos A, Janka Z, Kálmán J. · Alzheimer's Disease Research Centre, Department of Psychiatry, University of Szeged, 6 Semmelweis, H-6725 Szeged, Hungary. · Neurochem Int. · Pubmed #19428784 No free full text.

Abstract: Besides being an important component of spices used worldwide, capsaicin has wide-ranging therapeutic potential as a hypolipidemic, antioxidant and anti-inflammatory agent. Accordingly, it is very important to investigate the long-term effect of capsaicin in the pathogenesis of Alzheimer's disease. In this study, the effects of capsaicin on the processing of amyloid precursor protein (APP) were investigated in an in vivo model. The APP mRNA and protein levels were examined in the brain cortices of control and capsaicin-treated rats. The protein kinase C (PKC) translocation state in the soluble and membrane-bound fractions and the levels of beta-secretase (BACE) were also evaluated. Capsaicin enhanced the level of membrane-bound APP 1.7-fold. The APP mRNA and PKC and BACE protein levels were unchanged after capsaicin treatment. These in vivo data indicate that capsaicin is able to interfere with the brain APP metabolism by promoting the amyloidogenic route. We suggest that PKC is not involved in the mechanism underlying the effects.

Kálmán J, Palotás M, Pákáski M, Hugyecz M, Janka Z, Palotás A. · University of Szeged, Department of Psychiatry, Hungary. · Eur J Anaesthesiol. · Pubmed #16884554 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Recent studies emphasize a positive correlation between (cardiac) surgical interventions and increased risk for developing Alzheimer's disease in the late postoperative period. Since amyloid precursor protein and its neurotoxic derivatives play key roles in the development of Alzheimer's dementia, the impact of several agents used in the intra- and perioperative period is examined. METHOD: Amyloid precursor protein concentrations were assessed by semi-quantitative Western-immunoblot in brains of rats following intraperitoneal treatment with diazepam and midazolam. RESULTS: There were no significant changes in the amyloid precursor protein concentrations. CONCLUSION: Both diazepam and midazolam are considered to be relatively safe with respect to amyloid precursor protein metabolism.

Palotás M, Palotás A, Bjelik A, Pákáski M, Hugyecz M, Janka Z, Kálmán J. · Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6721, Szeged, Semmelweis u. 6, Hungary. · Neurochem Res. · Pubmed #16258851 No free full text.

Abstract: The incidence of Alzheimer's disease is elevated after exposure to surgical interventions. Since amyloid precursor protein (APP) and its neurotoxic derivatives play key roles in the development of Alzheimer dementia, the role of general anesthesia is controversial in the development of cognitive decline. As such, the effect of anesthetics on APP protein and mRNA levels was assessed utilizing semiquantitative Western-immunoblot and reverse transcription polymerase chain reaction (RT-PCR) in brains of rats following intraperitoneal treatment with propofol and thiopental. The anesthetics did not change cortical APP protein and mRNA concentration considerably. These results indicate that both propofol and thiopental are considered to be relatively safe with respect to APP metabolism.

Pákáski M, Bjelik A, Hugyecz M, Kása P, Janka Z, Kálmán J. · Alzheimer's Disease Research Centre, Department of Psychiatry, University of Szeged, Semmelweis 6, H-6725 Szeged, Hungary. · Neurochem Int. · Pubmed #15955598 No free full text.

Abstract: Comorbid depression of Alzheimer's disease (AD) is a common mood disorder in the elderly and a broad spectrum of antidepressants have been used for its treatment. Abeta peptides and other derivatives of the amyloid precursor protein (APP) have been implicated as central to the pathogenesis of AD. However, the functional relationship of APP and its proteolytic derivatives to antidepressant therapy is not known. In this study, Western blotting was used to test the ability of the tricyclic antidepressant (TCA) imipramine or the selective serotonin reuptake inhibitor (SSRI) citalopram to change the release of APP and the protein kinase C (PKC) content. Both antidepressants increased APP secretion in primary rat neuronal cultures. Imipramine or citalopram enhanced the level of secreted APP by 3.2- or 3.4-fold, respectively. Increases in PKC level were observed only after imipramine treatment. These in vitro data suggest that both TCA and SSRI are able to interfere with the APP metabolism. Imipramine promotes the non-amyloidogenic route of APP processing via stimulatory effects on PKC. We propose that PKC is not involved in the mechanism underlying the effects of citalopram on the APP metabolism. Since the secreted APP is not further available for the pathological cleavage of beta- and gamma-secretases, antidepressant medication might be beneficial in AD therapy.