TY - JOUR
T1 - DNA double strand breaks
T2 - A common theme in neurodegenerative diseases
AU - Merlo, Daniela
AU - Mollinari, Cristiana
AU - Racaniello, Mauro
AU - Garaci, Enrico
AU - Cardinale, Alessio
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Accumulation of DNA damage and impairment of DNA repair systems are involved in the pathogenesis of different neurodegenerative diseases. Whenever DNA damage is too extensive, the DNA damage response pathway provides for triggering cellular senescence and/or apoptosis. However, whether the increased level of DNA damage in neurodegenerative disorders is a cause rather than the consequence of neurodegenerative events remains to be established. Among possible DNA lesions, DNA double strand breaks (DSBs) are rare events, nevertheless they are the most lethal form of DNA damage. In neurons, DSBs are particularly deleterious because of their reduced DNA repair capability as compared to proliferating cells. Here, we provide a description of DSB repair systems and describe human studies showing the presence of several types of DNA lesions in three major neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Then, we analyze the role of DSB accumulation and deficiency of DSB repair systems in neurodegeneration by examining studies on animal models of neurodegenerative diseases.
AB - Accumulation of DNA damage and impairment of DNA repair systems are involved in the pathogenesis of different neurodegenerative diseases. Whenever DNA damage is too extensive, the DNA damage response pathway provides for triggering cellular senescence and/or apoptosis. However, whether the increased level of DNA damage in neurodegenerative disorders is a cause rather than the consequence of neurodegenerative events remains to be established. Among possible DNA lesions, DNA double strand breaks (DSBs) are rare events, nevertheless they are the most lethal form of DNA damage. In neurons, DSBs are particularly deleterious because of their reduced DNA repair capability as compared to proliferating cells. Here, we provide a description of DSB repair systems and describe human studies showing the presence of several types of DNA lesions in three major neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Then, we analyze the role of DSB accumulation and deficiency of DSB repair systems in neurodegeneration by examining studies on animal models of neurodegenerative diseases.
KW - Alzheimer’s disease
KW - DNA damage
KW - DNA double strand breaks
KW - DNA repair
KW - Huntington’s disease
KW - Neurodegenerative diseases
KW - Parkinson’s disease
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U2 - 10.2174/1567205013666160401114915
DO - 10.2174/1567205013666160401114915
M3 - Review article
AN - SCOPUS:84995752757
VL - 13
SP - 1208
EP - 1218
JO - Current Alzheimer Research
JF - Current Alzheimer Research
SN - 1567-2050
IS - 11
ER -