Brain Research Bulletin 75 (2008) 648–654 Research report Differences between normal and alpha-synuclein overexpressing SH-SY5Y neuroblastoma cells after A(1-42) and NAC treatment ´ Akos Hunya a,∗ , Istv´ an F ¨ oldi a,1 , Viktor Szegedi a,2 , Katalin So ´ os a,3 , M´ arta Zar´ andi a,3 , Antal Szab ´ o a,1 , D´ enes Z´ adori a,1 , Botond Penke a,b,4 , Zsolt L. Datki b,1 a Department of Medical Chemistry, University of Szeged, Szeged, Hungary b Supramolecular Research Group, Hungarian Academy of Sciences, Szeged, Hungary Received 4 June 2007; received in revised form 27 September 2007; accepted 22 October 2007 Available online 20 November 2007 Abstract Alpha-synuclein (SN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Intracellular inclusions containing aggregated SN have been reported in Alzheimer’s and Parkinson’s affected brains. Moreover, a proteolytic fragment of SN, the so-called non-amyloid component of Alzheimer’s disease amyloid (NAC) was found to be an integral part of Alzheimer’s dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of SN remains elusive. We have taken the advantage of an SN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H 2 O 2 , amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that SN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of SN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, SN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the SN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer’s and Parkinson’s disease. © 2007 Elsevier Inc. All rights reserved. Keywords: Alpha-synuclein; Beta-amyloid; NAC; SH-SY5Y; Alzheimer’s disease; Parkinson’s disease 1. Introduction The central pathological feature of Parkinson’s disease (PD) is the accumulation and aggregation of a synaptic protein, alpha- synclein (SN). Several findings underlie its main role, such as mutations in SN are associated with dominantly inher- ∗ Corresponding author at: H-6720 Szeged, Szikra utca 2, Hungary. Tel.: +36 62 546853; fax.: +36 62 546 826. E-mail addresses: akos.hunya@gmail.com ( ´ A. Hunya), istvanfoldi82@yahoo.com (I. F ¨ oldi), szegv@yahoo.com (V. Szegedi), soska@mdche.szote.u-szeged.hu (K. So ´ os), zarandimarta@yahoo.com (M. Zar´ andi), ertpar@freemail.hu (A. Szab´ o), zadorid@freemail.hu (D. Z´ adori), pbotond@mdche.szote.u-szeged.hu (B. Penke), datkiz@mdche.szote.u-szeged.hu (Z.L. Datki). 1 Tel.: +36 62 546853. 2 Tel.: +36 62 546854. 3 Tel.: +36 62 545140. 4 Tel.: +36 62 545 135. ited PD and SN was found to be the predominant protein in Lewy bodies [20,32,36]. Moreover, SN fibrillization appears to be a major event in other neurodegenerative diseases, such as multiple system atrophy, where SN is part of glial cyto- plasmic inclusions [37], and it is associated with the neuronal intranuclear inclusions of Huntington’s disease [5,15]. SN may even participate in the pathogenesis of Alzheimer’s disease (AD), because intracellular inclusions containing aggregated SN have been reported in Alzheimer’s affected brains [19,28]. In addition, a proteolytic fragment of SN, the so-called non- amyloid component of Alzheimer’s disease amyloid (NAC) was described as an integral part of plaques in demented patients [29]. The normal physiologic role of SN is under extensive research. It was cloned [38] and found to be a human homolog of the Torpedo ray synuclein, which had been previously iden- tified in synaptic vesicle preparations [27]. Taken its abundant expression in the nervous system and its close association with presynaptic vesicles [7,17], a role in vesicle refilling was sug- gested [1]. Moreover, SN undergoes a marked conformational 0361-9230/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2007.10.035