Alpha synuclein and its neurotoxic fragment NAC in neurodegeneration

• Autorzy: Adamczyk A. , Kazmierczak A. , Strosznajder J.
• Języki publikacji: EN

Abstrakty

EN

Alfa-Synuclein (ASN), a small (14 kDa) presynaptic protein abundant in the brain play signifi cant role in pathogenesis of Parkinson’s disease (PD) and is implicated in the other neurodegenerative disorders. The central domain of ASN, the non-amyloid β component of Alzheimer’s disease amyloid (NAC) could be responsible for its toxicity. Our study showed the signifi cant role of ASN/NAC in disturbance of dopamine transporter (DAT) and voltage-dependent calcium channels (VDCC) function in the brain. ASN-evoked disregulation of Ca2+ homeostasis leads to activation of neuronal nitric oxide synthase (nNOS). Our data indicated NO-dependent modifi cation of several proteins involved in decision of cell life/death including caspase-3 and poly(ADP-ribose) polymerase 1 (PARP-1). The further study carried out on cells in culture presented ASN/ NO dependent mitochondria failure and indicated that NO pool liberated by ASN activates caspase-3 that leads to PARP-1 degradation. Inhibitor of NOS (NNLA), caspase-3 (Z-DEVD-FMK) and a mitochondrial permeability transition pore blocker, cyclosporine A protected cells against ASN evoked cell death. Our results indicate that ASN/NAC leads to NO mediated mitochondria dysfunction and caspase-dependent programmed cell death. Supported by the Ministry of Science and Higher Education Grant 2PO5A4129 and Scientifi c Network 28/E-32/BWSN-0053/2008.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.286

Twórcy

autor

Adamczyk A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw

autor

Kazmierczak A.

• Department of Cellular Signaling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw

autor

Strosznajder J.

• Department of Cellular Signaling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw