Joanna B Strosznajder
Head of Department
Title: Poly(ADP-ribose)polymerases and sirtuins the promising targets for novel natural compounds against amyloidogenic proteins toxicity
Biography
Biography: Joanna B Strosznajder
Abstract
Poly(ADP-ribose) polymerases(PARPs) and Sirtuins (Sirts) are NAD+ dependent ezymes involved in regulation of energy homeostasis, genomic stability. The interplay between PARPs and Sirts is crucial in brain ischemia, Alzheimer’s Disease (AD) and other neurodegenerative disorders .Our recent study focused on the role of these enzymes in toxicity of amyloidogenic protein: amyloid beta (AB) and alpha synuclein (ASN) the key players in pathomechanism of AD. Our data indicated that inhibition of PARP-1-leads to activation of gene expression for Sirt1 and mitochondria Sirts (3,4,5) in PC12 cells. The inhibition of PARP-1 downregulated expression of beta secretase (BACE-1) the crucial enzyme in amyloidogenic metabolism of AB precursor protein (APP). This amyloidogenic pathway is activated by extracellular AB42 and ASN which upregulated expression of BACE-1 and also the subunits of secretase gamma. AB and ASN oligomers decreased the signaling pathways regulated by sphingosine kinase-1 and Akt kinase leading to apoptosis. Concomitantly, inhibition of Sirt1 and activation of genes for mitochondria Sirts and DNA bound PARPs occurred. Resveratrol and quercetin protect small population of cells against AB toxicity therefore it is a big request for the novel phytochemicals. We hope that PARPs and Sirts are very promising targets for novel therapeutic strategy of neurodegenerative disease.