Short communication Involvement of DNA damage and repair systems in neurodegenerative process Daniela Uberti, Giulia Ferrari Toninelli, Maurizio Memo * Department of Biomedical Sciences and Biotechnologies, University of Brescia, Via Valsabbina, 19, 25124 Brescia, Italy Abstract The study summarizes some recent data from our and other groups underlining the contribution to neurodegenera- tion of two transcription factors known to be involved in DNA damage sensing and repairing: the tumour suppressor gene p53 and the component of the DNA repair system MSH2. Both proteins participate in the cancer prevention machinery for the body as well as in the neurodegenerative process, suggesting that cancer and neurodegenerative disease may share common genetic risk factors for the development and progression of the disease. Here we show that, in neuronal cells, divergent cellular insults, i.e. the exposure to glutamate, b-amyloid (Ab) or H 2 O 2 , may converge to a common pathway that initiate with elevation of p53 protein levels. We also found that in SH-SY5Y neuronal cells H 2 O 2 induced the activation of DNA repair system with the nuclear translocation of MSH2, and PCNA. Differently no changes in MSH2 and PCNA cellular distribution were found in undifferentiating SH-SY5Y cells exposed to H 2 O 2 . This argues that defects in the repair of, or response to, DNA damage impact significantly on brain function. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: p53 gene product; Excitotoxicity; DNA damage/repair; Apoptosis 1. Introduction Preservation of genomic stability is an essential biological function. Cells engage very efficiently mechanisms involving DNA surveillance/repair proteins that work to maintaining inherited nu- cleotide sequence of genomic DNA over time. After DNA damage, that can arise both physiolo- gically and pathologically during duplication or after genotoxic stimuli, cells activate intracellular pathways which are able to recognize the damage, to arrest cell cycle, to recruit DNA repair factors, to repair the damage or induce apoptosis. This definitely relevant process is finalized to prevent the generation and the persistence of impaired cells which may ultimately be detrimental to the organism. Very little is known about the role of DNA damage sensors and repair factors in term- inally differentiated, not proliferating cells, like neurons. It is well recognized that mutation of genes related with DNA damage repair are associated with specific cancer-prone syndromes. Interest- ingly, as recently pointed out by Rolig and McKinnon (2000), many human pathological * Corresponding author. Tel.:  /39-030-371-7516; fax:  /39- 030-370-1157 E-mail address: memo@med.unibs.it (M. Memo). Toxicology Letters 139 (2003) 99  /105 www.elsevier.com/locate/toxlet 0378-4274/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0378-4274(02)00423-X