TY - JOUR
T1 - Nucleotide excision repair in chronic neurodegenerative diseases
AU - Sepe, Sara
AU - Payan-Gomez, Cesar
AU - Milanese, Chiara
AU - Hoeijmakers, Jan H.
AU - Mastroberardino, Pier G.
N1 - Funding Information:
PGM is supported by a grant from the Netherlands Genomics Initiative ( NGI/NWO 05040202 ), a Marie Curie grant ( IRG 247918 ), and the CEREBRAD grant under the EU-FP7 framework (project number 295552 ). JHJH acknowledges financial support of the National Institute of Health (NIH)/National Institute of Aging (NIA) ( 1PO1 AG-17242-02 ), NIEHS ( 1UO1 ES011044 ), the Royal Academy of Arts and Sciences of the Netherlands (academia professorship) and a European Research Council Advanced Grant . The research leading to these results has received funding from the European Community's Seventh Framework Program ( FP7/2007-2013 ) under grant agreement No. HEALTH-F2-2010-259893 . PGM is grateful to Dr. Laurie H. Sanders for constructive discussion on the role of DNA damage in neurodegenerative diseases.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/8
Y1 - 2013/8
N2 - Impaired DNA repair involving the nucleotide excision repair (NER)/transcription-coupled repair (TCR) pathway cause human pathologies associated with severe neurological symptoms. These clinical observations suggest that defective NER/TCR might also play a critical role in chronic neurodegenerative disorders (ND), such as Alzheimer's and Parkinson's disease. Involvement of NER/TCR in these disorders is also substantiated by the evidence that aging constitutes the principal risk factor for chronic ND and that this DNA repair mechanism is very relevant for the aging process itself. Our understanding of the exact role of NER/TCR in chronic ND, however, is extremely rudimentary; while there is no doubt that defective NER/TCR can lead to neuronal death, evidence for its participation in the etiopathogenesis of ND is inconclusive thus far. Here we summarize the experimental observations supporting a role for NER/TCR in chronic ND and suggest questions and lines of investigation that might help in addressing this important issue. We also present a preliminary yet unprecedented meta-analysis on human brain microarray data to understand the expression levels of the various NER factors in the anatomical areas relevant for chronic ND pathogenesis. In summary, this review intends to highlight elements supporting a role of NER/TCR in these devastating disorders and to propose potential strategies of investigation.
AB - Impaired DNA repair involving the nucleotide excision repair (NER)/transcription-coupled repair (TCR) pathway cause human pathologies associated with severe neurological symptoms. These clinical observations suggest that defective NER/TCR might also play a critical role in chronic neurodegenerative disorders (ND), such as Alzheimer's and Parkinson's disease. Involvement of NER/TCR in these disorders is also substantiated by the evidence that aging constitutes the principal risk factor for chronic ND and that this DNA repair mechanism is very relevant for the aging process itself. Our understanding of the exact role of NER/TCR in chronic ND, however, is extremely rudimentary; while there is no doubt that defective NER/TCR can lead to neuronal death, evidence for its participation in the etiopathogenesis of ND is inconclusive thus far. Here we summarize the experimental observations supporting a role for NER/TCR in chronic ND and suggest questions and lines of investigation that might help in addressing this important issue. We also present a preliminary yet unprecedented meta-analysis on human brain microarray data to understand the expression levels of the various NER factors in the anatomical areas relevant for chronic ND pathogenesis. In summary, this review intends to highlight elements supporting a role of NER/TCR in these devastating disorders and to propose potential strategies of investigation.
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U2 - 10.1016/j.dnarep.2013.04.009
DO - 10.1016/j.dnarep.2013.04.009
M3 - Research Article
C2 - 23726220
AN - SCOPUS:84880637848
SN - 1568-7864
VL - 12
SP - 568
EP - 577
JO - DNA Repair
JF - DNA Repair
IS - 8
ER -
