@article {27002,
	title = {Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology},
	journal = {Cell Rep},
	volume = {36},
	number = {10},
	year = {2021},
	note = {SenGupta, TanimaPalikaras, KonstantinosEsbensen, Ying QKonstantinidis, GeorgiosGalindo, Francisco Jose NaranjoAchanta, KavyaKassahun, HenokStavgiannoudaki, IoannaBohr, Vilhelm AAkbari, MansourGaare, JohannesTzoulis, CharalamposTavernarakis, NektariosNilsen, HildeengCell Rep. 2021 Sep 7;36(10):109668. doi: 10.1016/j.celrep.2021.109668.},
	month = {Sep 7},
	pages = {109668},
	edition = {2021/09/09},
	abstract = {Aging, genomic stress, and mitochondrial dysfunction are risk factors for neurodegenerative pathologies, such as Parkinson disease (PD). Although genomic instability is associated with aging and mitochondrial impairment, the underlying mechanisms are poorly understood. Here, we show that base excision repair generates genomic stress, promoting age-related neurodegeneration in a Caenorhabditis elegans PD model. A physiological level of NTH-1 DNA glycosylase mediates mitochondrial and nuclear genomic instability, which promote degeneration of dopaminergic neurons in older nematodes. Conversely, NTH-1 deficiency protects against alpha-synuclein-induced neurotoxicity, maintaining neuronal function with age. This apparent paradox is caused by modulation of mitochondrial transcription in NTH-1-deficient cells, and this modulation activates LMD-3, JNK-1, and SKN-1 and induces mitohormesis. The dependance of neuroprotection on mitochondrial transcription highlights the integration of BER and transcription regulation during physiological aging. Finally, whole-exome sequencing of genomic DNA from patients with idiopathic PD suggests that base excision repair might modulate susceptibility to PD in humans.},
	keywords = {Aging, base excision repair, C. elegans, DNA-glycosylase, hydrogen peroxide, mitohormesis, Neurodegeneration, Nth-1, oxidative DNA damage, Parkinson Disease},
	isbn = {2211-1247 (Electronic)},
	author = {SenGupta, T. and Palikaras, K. and Esbensen, Y. Q. and Konstantinidis, G. and Galindo, F. J. N. and Achanta, K. and Kassahun, H. and Stavgiannoudaki, I. and Bohr, V. A. and Akbari, M. and Gaare, J. and Tzoulis, C. and Tavernarakis, N. and Nilsen, H.}
}
