{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:03Z","timestamp":1792176003789,"version":"4.4.0"},"reference-count":216,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Helse S\u00f8r-\u00d8st RHF","award":["279922"],"award-info":[{"award-number":["279922"]}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["302483"],"award-info":[{"award-number":["302483"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson\u2019s disease (PD), Alzheimer\u2019s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.<\/jats:p>","DOI":"10.3390\/biology10020163","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T09:06:10Z","timestamp":1613725570000},"page":"163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases"],"prefix":"10.3390","volume":"10","author":[{"given":"Swapnil","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway"},{"name":"Section of Clinical Molecular Biology (EpiGen), Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"You","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway"},{"name":"Section of Clinical Molecular Biology (EpiGen), Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanima","family":"SenGupta","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway"},{"name":"Section of Clinical Molecular Biology (EpiGen), Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Nilsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway"},{"name":"Section of Clinical Molecular Biology (EpiGen), Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5226-4209","authenticated-orcid":false,"given":"Kulbhushan","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway"},{"name":"Department of Neurology, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3109\/10715762.2011.653968","article-title":"Chemical and biological consequences of oxidatively damaged guanine in DNA","volume":"46","author":"Delaney","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4344","DOI":"10.1172\/JCI65053","article-title":"8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair","volume":"122","author":"Sheng","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8935","DOI":"10.1038\/sj.onc.1205996","article-title":"Uracil in DNA-Occurrence, consequences and repair","volume":"21","author":"Krokan","year":"2002","journal-title":"Oncogene"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1021\/bi00769a018","article-title":"Rate of depurination of native deoxyribonucleic acid","volume":"11","author":"Lindahl","year":"1972","journal-title":"Biochemistry"},{"key":"ref_5","first-page":"124","article-title":"Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases","volume":"9","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/toxsci\/kfl125","article-title":"Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: Oxidation of thioredoxin and caspase-3 activation","volume":"95","author":"Ramachandiran","year":"2007","journal-title":"Toxicol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nature20411","article-title":"Ageing, neurodegeneration and brain rejuvenation","volume":"539","year":"2016","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nrm.2016.14","article-title":"Nuclear DNA damage signalling to mitochondria in ageing","volume":"17","author":"Fang","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00401-017-1726-6","article-title":"Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson\u2019s disease brain","volume":"134","author":"Trist","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.dnarep.2013.04.008","article-title":"DNA strand break repair and neurodegeneration","volume":"12","author":"Rulten","year":"2013","journal-title":"DNA Repair"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1128\/MCB.25.2.661-670.2005","article-title":"Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression","volume":"25","author":"Kang","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/cdd.2017.169","article-title":"How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?","volume":"25","author":"Aubrey","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/35044005","article-title":"The DNA damage response: Putting checkpoints in perspective","volume":"408","author":"Zhou","year":"2000","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/(SICI)1098-2280(1999)33:1<3::AID-EM2>3.0.CO;2-L","article-title":"Human DNA repair systems: An overview","volume":"33","author":"Yu","year":"1999","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1007\/s00018-009-8737-y","article-title":"DNA repair in mammalian cells: Nucleotide excision repair: Variations on versatility","volume":"66","author":"Nouspikel","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1093\/carcin\/22.7.987","article-title":"Base excision repair in a network of defence and tolerance","volume":"22","author":"Nilsen","year":"2001","journal-title":"Carcinogenesis"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/35077232","article-title":"Genome maintenance mechanisms for preventing cancer","volume":"411","author":"Hoeijmakers","year":"2001","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11244","DOI":"10.1093\/nar\/gkaa804","article-title":"Mechanisms of replication and repair in mitochondrial DNA deletion formation","volume":"48","author":"Fontana","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1093\/nar\/gkv472","article-title":"XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage","volume":"43","author":"Liu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1096\/fj.09-147991","article-title":"Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane","volume":"24","author":"Aamann","year":"2010","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1021\/acs.chemrestox.0c00083","article-title":"Mitochondrial DNA Damage: Prevalence, Biological Consequence, and Emerging Pathways","volume":"33","author":"Zhao","year":"2020","journal-title":"Chem. Res. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.dnarep.2008.06.018","article-title":"Comparison of nonhomologous end joining and homologous recombination in human cells","volume":"7","author":"Mao","year":"2008","journal-title":"DNA Repair"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/2041-9414-3-9","article-title":"Pathway choice in DNA double strand break repair: Observations of a balancing act","volume":"3","author":"Brandsma","year":"2012","journal-title":"Genome Integr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10502","DOI":"10.1074\/jbc.TM118.000371","article-title":"How cells ensure correct repair of DNA double-strand breaks","volume":"293","author":"Her","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/ncb2344","article-title":"More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance","volume":"13","author":"Lukas","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nair, N., Shoaib, M., and Sorensen, C.S. (2017). Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071486"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrm2514","article-title":"Ataxia-telangiectasia: From a rare disorder to a paradigm for cell signalling and cancer","volume":"9","author":"Lavin","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: Safeguarding genome integrity","volume":"3","author":"Shiloh","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: Making it safe to play with knives","volume":"40","author":"Ciccia","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1126\/science.281.5383.1674","article-title":"Enhanced phosphorylation of p53 by ATM in response to DNA damage","volume":"281","author":"Banin","year":"1998","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0092-8674(03)00566-X","article-title":"Histone H2AX: A dosage-dependent suppressor of oncogenic translocations and tumors","volume":"114","author":"Bassing","year":"2003","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.tibs.2011.10.002","article-title":"The ATM protein kinase and cellular redox signaling: Beyond the DNA damage response","volume":"37","author":"Ditch","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pizzamiglio, L., Focchi, E., and Antonucci, F. (2020). ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry. Cells, 9.","DOI":"10.3390\/cells9091969"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Anisenko, A., Kan, M., Shadrina, O., Brattseva, A., and Gottikh, M. (2020). Phosphorylation Targets of DNA-PK and Their Role in HIV-1 Replication. Cells, 9.","DOI":"10.3390\/cells9081907"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2013.01.007","article-title":"Mechanisms of programmed DNA lesions and genomic instability in the immune system","volume":"152","author":"Alt","year":"2013","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1172\/JCI67349","article-title":"PRKDC mutations in a SCID patient with profound neurological abnormalities","volume":"123","author":"Woodbine","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molcel.2015.02.024","article-title":"Differential phosphorylation of DNA-PKcs regulates the interplay between end-processing and end-ligation during nonhomologous end-joining","volume":"58","author":"Jiang","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1101\/gad.1067403","article-title":"Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance","volume":"17","author":"Brown","year":"2003","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA damage, repair, and mutagenesis","volume":"58","author":"Chatterjee","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ajhg.2008.01.009","article-title":"The involvement of DNA-damage and -repair defects in neurological dysfunction","volume":"82","author":"Kulkarni","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1212\/WNL.0000000000004989","article-title":"DNA damage response: Selected review and neurologic implications","volume":"90","author":"Coon","year":"2018","journal-title":"Neurology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","article-title":"Trinucleotide repeat disorders","volume":"30","author":"Orr","year":"2007","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.cell.2015.07.003","article-title":"Identification of Genetic Factors that Modify Clinical Onset of Huntington\u2019s Disease","volume":"162","author":"Lee","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrg2828","article-title":"Mechanisms of trinucleotide repeat instability during human development","volume":"11","author":"McMurray","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nsmb959","article-title":"Slipped (CTG)*(CAG) repeats can be correctly repaired, escape repair or undergo error-prone repair","volume":"12","author":"Panigrahi","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Massey, T.H., and Jones, L. (2018). The central role of DNA damage and repair in CAG repeat diseases. Dis. Model. Mech., 11.","DOI":"10.1242\/dmm.031930"},{"key":"ref_51","first-page":"395","article-title":"Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex","volume":"26","author":"Maiuri","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Gao, R., Liu, Y., Silva-Fernandes, A., Fang, X., Paulucci-Holthauzen, A., Chatterjee, A., Zhang, H.L., Matsuura, T., Choudhary, S., and Ashizawa, T. (2015). Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1004834"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8326","DOI":"10.1093\/nar\/gky641","article-title":"Combined deficiency of Senataxin and DNA-PKcs causes DNA damage accumulation and neurodegeneration in spinal muscular atrophy","volume":"46","author":"Kannan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/brain\/awz373","article-title":"ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy","volume":"143","author":"Kannan","year":"2020","journal-title":"Brain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00002093-200210000-00001","article-title":"Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank","volume":"16","author":"Barker","year":"2002","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"470S","DOI":"10.1093\/ajcn\/83.2.470S","article-title":"Inflammation and neurodegenerative diseases","volume":"83","author":"Griffin","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.disamonth.2010.06.001","article-title":"Alzheimer disease","volume":"56","author":"Castellani","year":"2010","journal-title":"Dis. Mon."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.bcp.2013.12.024","article-title":"Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers","volume":"88","author":"Reitz","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1586\/14737175.7.7.887","article-title":"Environmental and dietary risk factors in Alzheimer\u2019s disease","volume":"7","author":"Dosunmu","year":"2007","journal-title":"Expert Rev. Neurother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/325733a0","article-title":"The precursor of Alzheimer\u2019s disease amyloid A4 protein resembles a cell-surface receptor","volume":"325","author":"Kang","year":"1987","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/375754a0","article-title":"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer\u2019s disease","volume":"375","author":"Sherrington","year":"1995","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.7638622","article-title":"Candidate gene for the chromosome 1 familial Alzheimer\u2019s disease locus","volume":"269","author":"Wasco","year":"1995","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1001\/archneurol.2011.221","article-title":"Autosomal recessive causes likely in early-onset Alzheimer disease","volume":"69","author":"Wingo","year":"2012","journal-title":"Arch. Neurol"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1172\/JCI24761","article-title":"The genetic epidemiology of neurodegenerative disease","volume":"115","author":"Bertram","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.neurobiolaging.2003.12.023","article-title":"ApoE genotype accounts for the vast majority of AD risk and AD pathology","volume":"25","author":"Raber","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0006-8993(99)02004-1","article-title":"DNA strand breaks in Alzheimer\u2019s disease","volume":"849","author":"Adamec","year":"1999","journal-title":"Brain Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11357-008-9050-7","article-title":"Evidence of DNA damage in Alzheimer disease: Phosphorylation of histone H2AX in astrocytes","volume":"30","author":"Myung","year":"2008","journal-title":"Age"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40478-019-0723-5","article-title":"Early neuronal accumulation of DNA double strand breaks in Alzheimer\u2019s disease","volume":"7","author":"Shanbhag","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1046\/j.1471-4159.1998.71052034.x","article-title":"Increased nuclear DNA oxidation in the brain in Alzheimer\u2019s disease","volume":"71","author":"Gabbita","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1046\/j.1471-4159.1997.68052061.x","article-title":"An assessment of oxidative damage to proteins, lipids, and DNA in brain from patients with Alzheimer\u2019s disease","volume":"68","author":"Lyras","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shen, X., Chen, J., Li, J., Kofler, J., and Herrup, K. (2016). Neurons in Vulnerable Regions of the Alzheimer\u2019s Disease Brain Display Reduced ATM Signaling. eNeuro, 3.","DOI":"10.1523\/ENEURO.0124-15.2016"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8897","DOI":"10.1038\/ncomms9897","article-title":"DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice","volume":"6","author":"Suberbielle","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.29245\/2572.942X\/2016\/3.1016","article-title":"DNA-PK Deficiency in Alzheimer\u2019s Disease","volume":"1","author":"Kanungo","year":"2016","journal-title":"J. Neurol. Neuromedicine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0006-8993(99)02335-5","article-title":"Decreased base excision repair and increased helicase activity in Alzheimer\u2019s disease brain","volume":"855","author":"Lovell","year":"2000","journal-title":"Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1093\/nar\/gkm605","article-title":"Defective DNA base excision repair in brain from individuals with Alzheimer\u2019s disease and amnestic mild cognitive impairment","volume":"35","author":"Weissman","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.neurobiolaging.2014.01.004","article-title":"Base excision DNA repair levels in mitochondrial lysates of Alzheimer\u2019s disease","volume":"35","author":"Canugovi","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1749-6632.2001.tb05641.x","article-title":"DNA polymerase-beta may be the main player for defective DNA repair in aging rat neurons","volume":"928","author":"Rao","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/em.22206","article-title":"Loss of DNA polymerase beta induces cellular senescence","volume":"59","author":"Ahmed","year":"2018","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/nar\/gku1356","article-title":"DNA polymerase beta deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes","volume":"43","author":"Sykora","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.3389\/fimmu.2018.01283","article-title":"The Role of Mitophagy in Innate Immunity","volume":"9","author":"Gkikas","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1093\/brain\/awz191","article-title":"Genetic analysis of Mendelian mutations in a large UK population-based Parkinson\u2019s disease study","volume":"142","author":"Tan","year":"2019","journal-title":"Brain"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gaare, J.J., Nido, G., Dolle, C., Sztromwasser, P., Alves, G., Tysnes, O.B., Haugarvoll, K., and Tzoulis, C. (2020). Meta-analysis of whole-exome sequencing data from two independent cohorts finds no evidence for rare variant enrichment in Parkinson disease associated loci. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239824"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1046\/j.1471-4159.1997.69031196.x","article-title":"Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra","volume":"69","author":"Alam","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.abb.2006.02.018","article-title":"Studies on genomic DNA topology and stability in brain regions of Parkinson\u2019s disease","volume":"449","author":"Hegde","year":"2006","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.brainres.2006.11.072","article-title":"Increased 8-OHdG levels in the urine, serum, and substantia nigra of hemiparkinsonian rats","volume":"1133","author":"Yasuhara","year":"2007","journal-title":"Brain Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.celrep.2016.04.071","article-title":"Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson\u2019s Disease","volume":"15","author":"Sepe","year":"2016","journal-title":"Cell Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00401-006-0081-9","article-title":"Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson\u2019s disease","volume":"112","author":"Arai","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/jnr.21191","article-title":"Oxidative damage in nucleic acids and Parkinson\u2019s disease","volume":"85","author":"Nakabeppu","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s00401-004-0937-9","article-title":"Expression of 8-oxoguanine DNA glycosylase (OGG1) in Parkinson\u2019s disease and related neurodegenerative disorders","volume":"109","author":"Fukae","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.neuint.2012.06.013","article-title":"Ogg1 null mice exhibit age-associated loss of the nigrostriatal pathway and increased sensitivity to MPTP","volume":"61","author":"Nevin","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/mc.22495","article-title":"Polyubiquitination of apurinic\/apyrimidinic endonuclease 1 by Parkin","volume":"56","author":"Scott","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.nbd.2014.06.014","article-title":"Mitochondrial DNA damage: Molecular marker of vulnerable nigral neurons in Parkinson\u2019s disease","volume":"70","author":"Sanders","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1089\/gtmb.2011.0252","article-title":"DNA repair genes in Parkinson\u2019s disease","volume":"16","author":"Gencer","year":"2012","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1093\/toxsci\/kfx086","article-title":"Editor\u2019s Highlight: Base Excision Repair Variants and Pesticide Exposure Increase Parkinson\u2019s Disease Risk","volume":"158","author":"Sanders","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ng.3955","article-title":"A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci","volume":"49","author":"Chang","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: A meta-analysis of genome-wide association studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S133","DOI":"10.3233\/JAD-170342","article-title":"Chromatin-Bound Oxidized alpha-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson\u2019s Disease","volume":"60","author":"Vasquez","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kam, T.I., Mao, X., Park, H., Chou, S.C., Karuppagounder, S.S., Umanah, G.E., Yun, S.P., Brahmachari, S., Panicker, N., and Chen, R. (2018). Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson\u2019s disease. Science, 362.","DOI":"10.1126\/science.aat8407"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"532","DOI":"10.3389\/fnins.2019.00532","article-title":"Motor Neuron Susceptibility in ALS\/FTD","volume":"13","author":"Ragagnin","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbadis.2014.08.010","article-title":"Sporadic and hereditary amyotrophic lateral sclerosis (ALS)","volume":"1852","author":"Siddique","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1172\/JCI71601","article-title":"Emerging mechanisms of molecular pathology in ALS","volume":"125","author":"Peters","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1002\/jcb.24234","article-title":"Early pathogenesis in the adult-onset neurodegenerative disease amyotrophic lateral sclerosis","volume":"113","author":"Izaurieta","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/archneur.1982.00510230003001","article-title":"A new hypothesis of the etiology of amyotrophic lateral sclerosis. The DNA hypothesis","volume":"39","author":"Bradley","year":"1982","journal-title":"Arch. Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-019-0874-4","article-title":"DNA damage accumulates and responses are engaged in human ALS brain and spinal motor neurons and DNA repair is activatable in iPSC-derived motor neurons with SOD1 mutations","volume":"8","author":"Kim","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1046\/j.1471-4159.1997.69052064.x","article-title":"Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis","volume":"69","author":"Ferrante","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/362059a0","article-title":"Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis","volume":"362","author":"Rosen","year":"1993","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1093\/brain\/aww033","article-title":"NEK1 mutations in familial amyotrophic lateral sclerosis","volume":"139","author":"Brenner","year":"2016","journal-title":"Brain"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4161\/cc.10.4.14814","article-title":"Nek1 kinase functions in DNA damage response and checkpoint control through a pathway independent of ATM and ATR","volume":"10","author":"Chen","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.scr.2018.06.005","article-title":"NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons","volume":"30","author":"Higelin","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12017-002-0038-7","article-title":"DNA base-excision repair enzyme apurinic\/apyrimidinic endonuclease\/redox factor-1 is increased and competent in the brain and spinal cord of individuals with amyotrophic lateral sclerosis","volume":"2","author":"Shaikh","year":"2002","journal-title":"Neuromol. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.brainres.2007.02.057","article-title":"Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of presymptomatic transgenic mice carrying a mutant SOD1 gene","volume":"1150","author":"Murakami","year":"2007","journal-title":"Brain Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"24731","DOI":"10.1074\/jbc.M113.497974","article-title":"The RNA-binding protein fused in sarcoma (FUS) functions downstream of poly(ADP-ribose) polymerase (PARP) in response to DNA damage","volume":"288","author":"Mastrocola","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/nar\/gkt835","article-title":"PARP-1 dependent recruitment of the amyotrophic lateral sclerosis-associated protein FUS\/TLS to sites of oxidative DNA damage","volume":"42","author":"Rulten","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nn.3514","article-title":"Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons","volume":"16","author":"Wang","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nsmb.1899","article-title":"Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining","volume":"17","author":"Miller","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13024-020-00365-9","article-title":"Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS\/FTD","volume":"15","author":"Andrade","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1093\/hmg\/ddx170","article-title":"The DNA damage response (DDR) is induced by the C9orf72 repeat expansion in amyotrophic lateral sclerosis","volume":"26","author":"Farg","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"E656","DOI":"10.1073\/pnas.1110470109","article-title":"ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila","volume":"109","author":"Petersen","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/jnr.21881","article-title":"DNA breakage and induction of DNA damage response proteins precede the appearance of visible mutant huntingtin aggregates","volume":"87","author":"Illuzzi","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"268ra178","DOI":"10.1126\/scitranslmed.3010523","article-title":"Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington\u2019s disease","volume":"6","author":"Lu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41419-018-0848-7","article-title":"Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson\u2019s disease","volume":"9","author":"Milanese","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"E9645","DOI":"10.1073\/pnas.1707151114","article-title":"Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer\u2019s disease","volume":"114","author":"Mano","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.bbadis.2011.08.005","article-title":"Aging and amyloid beta-induced oxidative DNA damage and mitochondrial dysfunction in Alzheimer\u2019s disease: Implications for early intervention and therapeutics","volume":"1812","author":"Mao","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kurihara, M., Mano, T., Saito, Y., Murayama, S., Toda, T., and Iwata, A. (2019). Colocalization of BRCA1 with Tau Aggregates in Human Tauopathies. Brain Sci., 10.","DOI":"10.3390\/brainsci10010007"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1093\/jnen\/nlz107","article-title":"Aberrant Accumulation of BRCA1 in Alzheimer Disease and Other Tauopathies","volume":"79","author":"Nakamura","year":"2020","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/JAD-170830","article-title":"Overactive BRCA1 Affects Presenilin 1 in Induced Pluripotent Stem Cell-Derived Neurons in Alzheimer\u2019s Disease","volume":"62","author":"Wezyk","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13024-015-0023-x","article-title":"Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS","volume":"10","author":"Noristani","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0027-5107(02)00222-1","article-title":"DNA repair in neural cells: Basic science and clinical implications","volume":"509","author":"Brooks","year":"2002","journal-title":"Mutat. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.neurobiolaging.2005.03.009","article-title":"DNA end joining activity is reduced in Alzheimer\u2019s disease","volume":"27","author":"Shackelford","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0197-4580(02)00229-4","article-title":"Is DNA repair compromised in Alzheimer\u2019s disease?","volume":"24","author":"Davydov","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1074\/jbc.M111.276550","article-title":"Sublethal doses of beta-amyloid peptide abrogate DNA-dependent protein kinase activity","volume":"287","author":"Cardinale","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1093\/nar\/gkp229","article-title":"Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites","volume":"37","author":"Altmeyer","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"308","DOI":"10.2741\/707","article-title":"Involvement of PARPs in cell death","volume":"6","author":"Aredia","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.2741\/2909","article-title":"The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases","volume":"13","author":"Hassa","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fmolb.2020.00191","article-title":"Poly(ADP-Ribose) Glycohydrolase (PARG) vs. Poly(ADP-Ribose) Polymerase (PARP)\u2014Function in Genome Maintenance and Relevance of Inhibitors for Anti-cancer Therapy","volume":"7","author":"Harrision","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fgene.2012.00169","article-title":"Regulation of chromatin structure by poly(ADP-ribosyl)ation","volume":"3","author":"Beneke","year":"2012","journal-title":"Front. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.mam.2012.12.010","article-title":"Poly(ADP-ribose): PARadigms and PARadoxes","volume":"34","author":"Burkle","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.cmet.2016.09.004","article-title":"NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair","volume":"24","author":"Fang","year":"2016","journal-title":"Cell Metab."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1523\/JNEUROSCI.5552-09.2010","article-title":"NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death","volume":"30","author":"Alano","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/15384101.2017.1285631","article-title":"NAD(+) in DNA repair and mitochondrial maintenance","volume":"16","author":"Croteau","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/brain\/122.2.247","article-title":"Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer\u2019s disease","volume":"122 Pt 2","author":"Love","year":"1999","journal-title":"Brain"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1742-2094-8-152","article-title":"Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid beta","volume":"8","author":"Kauppinen","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Martire, S., Fuso, A., Rotili, D., Tempera, I., Giordano, C., De Zottis, I., Muzi, A., Vernole, P., Graziani, G., and Lococo, E. (2013). PARP-1 modulates amyloid beta peptide-induced neuronal damage. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072169"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","article-title":"Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer\u2019s disease","volume":"22","author":"Fang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1073\/pnas.96.10.5774","article-title":"Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism","volume":"96","author":"Mandir","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00401-009-0580-6","article-title":"Persistent cleavage and nuclear translocation of apoptosis-inducing factor in motor neurons in the spinal cord of sporadic amyotrophic lateral sclerosis patients","volume":"118","author":"Shibata","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40478-018-0586-1","article-title":"Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis","volume":"6","author":"McGurk","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neulet.2006.07.044","article-title":"AIF translocates to the nucleus in the spinal motor neurons in a mouse model of ALS","volume":"406","author":"Oh","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1016\/j.celrep.2018.05.009","article-title":"The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson\u2019s Disease","volume":"23","author":"Schondorf","year":"2018","journal-title":"Cell Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrn3961","article-title":"Compromised autophagy and neurodegenerative diseases","volume":"16","author":"Menzies","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_153","first-page":"2190","article-title":"The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice","volume":"118","author":"Pickford","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nm.3232","article-title":"The role of autophagy in neurodegenerative disease","volume":"19","author":"Nixon","year":"2013","journal-title":"Nat. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"23542","DOI":"10.1074\/jbc.M801992200","article-title":"Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells","volume":"283","author":"Vogiatzi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/21678421.2016.1218517","article-title":"A novel amyotrophic lateral sclerosis mutation in OPTN induces ER stress and Golgi fragmentation in vitro","volume":"18","author":"Fifita","year":"2017","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1242\/jcs.114926","article-title":"Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates","volume":"126","author":"Korac","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1080\/15548627.2016.1170257","article-title":"Defective recognition of LC3B by mutant SQSTM1\/p62 implicates impairment of autophagy as a pathogenic mechanism in ALS-FTLD","volume":"12","author":"Goode","year":"2016","journal-title":"Autophagy"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/nature09803","article-title":"HDACs link the DNA damage response, processing of double-strand breaks and autophagy","volume":"471","author":"Robert","year":"2011","journal-title":"Nature"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.4161\/auto.20519","article-title":"Autophagy acts as a safeguard mechanism against G-quadruplex ligand-mediated DNA damage","volume":"8","author":"Orlotti","year":"2012","journal-title":"Autophagy"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/auto.23280","article-title":"DNA damage signaling triggers the cytoplasm-to-vacuole pathway of autophagy to regulate cell cycle progression","volume":"9","author":"Eapen","year":"2013","journal-title":"Autophagy"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1073\/pnas.0913860107","article-title":"ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS","volume":"107","author":"Alexander","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"672","DOI":"10.4161\/auto.6.5.12509","article-title":"ATM engages the TSC2\/mTORC1 signaling node to regulate autophagy","volume":"6","author":"Alexander","year":"2010","journal-title":"Autophagy"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Cheng, A., Tse, K.H., Chow, H.M., Gan, Y., Song, X., Ma, F., Qian, Y.X.Y., She, W., and Herrup, K. (2020). ATM loss disrupts the autophagy-lysosomal pathway. Autophagy, 1\u201313.","DOI":"10.1080\/15548627.2020.1805860"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/cr.2012.70","article-title":"ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy","volume":"22","author":"Rodriguez","year":"2012","journal-title":"Cell Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"45385","DOI":"10.1038\/srep45385","article-title":"Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1038\/ncomms3674","article-title":"Base excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy","volume":"4","author":"SenGupta","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1080\/15548627.2016.1210368","article-title":"SQSTM1\/p62 mediates crosstalk between autophagy and the UPS in DNA repair","volume":"12","author":"Hewitt","year":"2016","journal-title":"Autophagy"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"6823","DOI":"10.1038\/ncomms7823","article-title":"Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage","volume":"6","author":"Park","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.4161\/auto.21035","article-title":"UVRAG: At the crossroad of autophagy and genomic stability","volume":"8","author":"Zhao","year":"2012","journal-title":"Autophagy"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1093\/nar\/gkaa393","article-title":"DNA damage invokes mitophagy through a pathway involving Spata18","volume":"48","author":"Dan","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1080\/15548627.2019.1582973","article-title":"Radiation induces EIF2AK3\/PERK and ERN1\/IRE1 mediated pro-survival autophagy","volume":"15","author":"Chaurasia","year":"2019","journal-title":"Autophagy"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd1330","article-title":"Neurodegenerative diseases and oxidative stress","volume":"3","author":"Barnham","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.3389\/fphar.2019.01008","article-title":"Neuroinflammation as a Common Feature of Neurodegenerative Disorders","volume":"10","author":"Maccioni","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.redox.2015.05.008","article-title":"Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage\/repair","volume":"5","author":"Mikhed","year":"2015","journal-title":"Redox Biol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1093\/carcin\/bgu066","article-title":"hOGG1-Cys326 variant cells are hypersensitive to DNA repair inhibition by nitric oxide","volume":"35","author":"Moritz","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1152\/jn.00848.2018","article-title":"Neuroinflammation and the cGAS-STING pathway","volume":"121","author":"Chin","year":"2019","journal-title":"J. Neurophysiol."},{"key":"ref_179","first-page":"109","article-title":"A rat model of ataxia-telangiectasia: Evidence for a neurodegenerative phenotype","volume":"26","author":"Quek","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.bbi.2019.07.004","article-title":"Efficacy and mechanism of cGAMP to suppress Alzheimer\u2019s disease by elevating TREM2","volume":"81","author":"Xu","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","article-title":"TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS\/STING in ALS","volume":"183","author":"Yu","year":"2020","journal-title":"Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1093\/brain\/awaa246","article-title":"Mitochondrial damage-associated inflammation highlights biomarkers in PRKN\/PINK1 parkinsonism","volume":"143","author":"Borsche","year":"2020","journal-title":"Brain"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"16208","DOI":"10.1523\/JNEUROSCI.2911-10.2010","article-title":"Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy","volume":"30","author":"Liachko","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.cell.2014.03.026","article-title":"Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)\/SIRT1 reduction","volume":"157","author":"Fang","year":"2014","journal-title":"Cell"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/ana.23946","article-title":"Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis","volume":"74","author":"Ciura","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.biocel.2004.10.015","article-title":"Molecular cloning and functional characterization of zebrafish ATM","volume":"37","author":"Imamura","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1046\/j.1471-4159.2003.01809.x","article-title":"Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein","volume":"86","author":"Lakso","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Van Ham, T.J., Thijssen, K.L., Breitling, R., Hofstra, R.M., Plasterk, R.H., and Nollen, E.A. (2008). C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000027"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1750-1326-7-57","article-title":"Utility of an improved model of amyloid-beta (Abeta(1)(-)(4)(2)) toxicity in Caenorhabditis elegans for drug screening for Alzheimer\u2019s disease","volume":"7","author":"McColl","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"13102","DOI":"10.1523\/JNEUROSCI.3448-06.2006","article-title":"Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans","volume":"26","author":"Wu","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"165876","DOI":"10.1016\/j.bbadis.2020.165876","article-title":"TDP-1\/TDP-43 potentiates human alpha-Synuclein (HASN) neurodegeneration in Caenorhabditis elegans","volume":"1866","author":"Shen","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrn751","article-title":"Modelling neurodegenerative diseases in Drosophila: A fruitful approach?","volume":"3","author":"Muqit","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Pitchai, A., Rajaretinam, R.K., and Freeman, J.L. (2019). Zebrafish as an Emerging Model for Bioassay-Guided Natural Product Drug Discovery for Neurological Disorders. Medicines, 6.","DOI":"10.3390\/medicines6020061"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41420-018-0109-7","article-title":"Zebrafish: An emerging real-time model system to study Alzheimer\u2019s disease and neurospecific drug discovery","volume":"4","author":"Saleem","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s11910-011-0182-2","article-title":"Modeling neurodegeneration in zebrafish","volume":"11","author":"Xi","year":"2011","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"102669","DOI":"10.1016\/j.dnarep.2019.102669","article-title":"DNA repair and neurological disease: From molecular understanding to the development of diagnostics and model organisms","volume":"81","author":"Abugable","year":"2019","journal-title":"DNA Repair"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10821","article-title":"Probing sporadic and familial Alzheimer\u2019s disease using induced pluripotent stem cells","volume":"482","author":"Israel","year":"2012","journal-title":"Nature"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1248\/bpb.b17-00364","article-title":"Nobiletin Reduces Intracellular and Extracellular beta-Amyloid in iPS Cell-Derived Alzheimer\u2019s Disease Model Neurons","volume":"41","author":"Kimura","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.stemcr.2017.02.019","article-title":"Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis","volume":"8","author":"Bhinge","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41467-017-02299-1","article-title":"Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation","volume":"9","author":"Naumann","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fnins.2018.00086","article-title":"Modeling Protein Aggregation and the Heat Shock Response in ALS iPSC-Derived Motor Neurons","volume":"12","author":"Seminary","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1038\/s41467-020-17165-w","article-title":"Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson\u2019s disease","volume":"11","author":"Doi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s12974-016-0761-x","article-title":"Mutations in LRRK2 impair NF-kappaB pathway in iPSC-derived neurons","volume":"13","author":"Lang","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.neuron.2018.06.011","article-title":"APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer\u2019s Disease Phenotypes in Human iPSC-Derived Brain Cell Types","volume":"98","author":"Lin","year":"2018","journal-title":"Neuron"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molmed.2017.02.007","article-title":"Disease Modeling in Stem Cell-Derived 3D Organoid Systems","volume":"23","author":"Dutta","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1038\/s41467-018-06684-2","article-title":"Microglia innately develop within cerebral organoids","volume":"9","author":"Ormel","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1089\/ten.tea.2017.0423","article-title":"Modeling Neurodegenerative Microenvironment Using Cortical Organoids Derived from Human Stem Cells","volume":"24","author":"Yan","year":"2018","journal-title":"Tissue Eng. Part A"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1038\/s41380-018-0229-8","article-title":"Modeling amyloid beta and tau pathology in human cerebral organoids","volume":"23","author":"Gonzalez","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41380-019-0468-3","article-title":"Modeling Alzheimer\u2019s disease with iPSC-derived brain cells","volume":"25","author":"Penney","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.stemcr.2019.01.020","article-title":"Modeling G2019S-LRRK2 Sporadic Parkinson\u2019s Disease in 3D Midbrain Organoids","volume":"12","author":"Kim","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.stemcr.2017.03.010","article-title":"Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells","volume":"8","author":"Monzel","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41531-019-0078-4","article-title":"Modeling Parkinson\u2019s disease in midbrain-like organoids","volume":"5","author":"Smits","year":"2019","journal-title":"NPJ Parkinsons Dis."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1038\/s41598-018-23512-1","article-title":"Engineered 3D vascular and neuronal networks in a microfluidic platform","volume":"8","author":"Osaki","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nrn3983","article-title":"A genetic cause of Alzheimer disease: Mechanistic insights from Down syndrome","volume":"16","author":"Wiseman","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1136\/jnnp.59.1.90","article-title":"Sequence of the superoxide dismutase 1 (SOD 1) gene in familial Parkinson\u2019s disease","volume":"59","author":"Bandmann","year":"1995","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"11648","DOI":"10.1074\/jbc.M414327200","article-title":"Oxidative modifications and aggregation of Cu,Zn-superoxide dismutase associated with Alzheimer and Parkinson diseases","volume":"280","author":"Choi","year":"2005","journal-title":"J. Biol. Chem."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/2\/163\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:26:06Z","timestamp":1760160366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/2\/163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,19]]},"references-count":216,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["biology10020163"],"URL":"https:\/\/doi.org\/10.3390\/biology10020163","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,19]]}}}