Journal: Cell Reports

Article Title: Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology

doi: 10.1016/j.celrep.2021.109668

Figure Lengend Snippet: NTH-1 deficiency protects against α-synuclein neurotoxicity in a C. elegans Parkinson disease model (A) Schematic of the BER pathway. (B–D) Transgenic nematodes co-expressing human α-synuclein (α-syn) and cytoplasmic GFP in dopaminergic (DA) neurons display progressive degeneration with age. NTH-1 deficiency confers resistance to neuronal loss. (B) Images of the head (CEPs and ADEs) and middle body (PDEs) region of BY273 animals show age-related deterioration of DA neuronal cells. Age-dependent neurodegeneration is abolished in nth-1; BY273 mutants (scale bar, 5 μm, 63× objective). (C) The column scatterplot represents GFP intensity of the CEPs, ADEs, and PDEs dopaminergic neurons in young day 1 and old day 7 nematodes in both BY273 and nth-1; BY273 animals (n = 30 from three independent experiments; ∗∗∗ p < 0.001; one-way ANOVA followed by Bonferroni’s multiple comparison test). (D) Survival of anterior CEPs and ADEs DA neurons of BY273 and nth-1; BY273 nematodes during aging (n = 35 nematodes per group; ∗∗∗ p < 0.001; one-way ANOVA followed by Šidák’s multiple-comparisons test). Representative images of the head region of BY273 and nth-1; BY273 mutants at day 7 of adulthood. Remnants of neuronal cell bodies and axonal beading are scored in BY273 animals. Neuronal soma and processes architecture are maintained in NTH-1-deficient PD nematodes (scale bar, 50 μm). (E) The column scatterplots represent GFP intensity of the CEPs and ADEsand PDEs DA neurons in both BY273 and nth-1; BY273 animals in response to 6-OHDA (30 mM) and MPP + (2 mM); n = 30 from three independent experiments; ∗∗ p < 0.01, ∗∗∗ p < 0.001; one-way ANOVA followed by Bonferroni’s multiple comparison test. The corresponding fluorescence image is depicted in Figure S1 B. Error bars, SEM.

Article Snippet: pPD96.52 , Addgene , Fire lab C. elegans vector kit.

Techniques: Transgenic Assay, Expressing, Fluorescence

Journal: Cell Reports

Article Title: Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology

doi: 10.1016/j.celrep.2021.109668

Figure Lengend Snippet: BER act as a susceptibility modifier in C. elegans PD animals Age-dependent accumulation of mitochondrial and nuclear DNA repair intermediates are generated through incomplete repair of endogenous base damage via the BER pathway. These repair intermediates promote DA neuronal vulnerability and degeneration in wild-type PD animals. In NTH-1-deficient nematodes, BER generated repair intermediates are not generated, but a state of mild mitochondrial dysfunction is induced, resulting in elevated H 2 O 2 levels through the activity of SODs. In turn, SKN-1, LMD-3, and JNK-1 are stimulated to orchestrate a response that protects DA neurons from α-syn induced neurotoxicity via mitohormesis.

Article Snippet: pPD96.52 , Addgene , Fire lab C. elegans vector kit.

Techniques: Generated, Activity Assay

Journal: Cell Reports

Article Title: Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology

doi: 10.1016/j.celrep.2021.109668

Figure Lengend Snippet:

Article Snippet: pPD96.52 , Addgene , Fire lab C. elegans vector kit.

Techniques: Recombinant, TUNEL Assay, Plasmid Preparation, Software, Microscopy, Imaging