In contrast, when ARH3-deficient neural cells encounter additional stressors (e.g., viral infection or environmental stressors) (Ghosh et al., 2018; Grady et al., 2012), they may accumulate extreme levels of PARylation that shortly overwhelm cell tolerance (Figure 6E, top), disrupting chromatin modification and transcription states and eventually leading to PARP-dependent cell death. The gene discussed is PARP1; the disease is viral infectious disease.