Neurodegenerative diseases induce a slow form of cell death that is inconsistent with either apoptosis or necrosis. Hoshino et al. (page 589) describe a novel slow form of cell death caused by transcriptional repression, a dysfunction associated with neurons in the polyglutamine diseases.
Primary neurons grown in culture in the presence of α-amanitin, a chemical repressor of transcription, survived for five days, whereas treated nonneuronal cells underwent apoptotic death within 12 hours. When the neurons finally did die, their demise did not resemble apoptosis, necrosis, or autophagy, in terms of morphology, biochemical characteristics, or DNA breakdown.
YAP, a cotranscription factor that works with p73 to induce transcription of proapoptotic genes, was highly expressed in cells undergoing this slow transcriptional repression induced atypical death (TRIAD). However, the forms of YAP protein expressed in these neurons, YAPΔCs, lacked the transcriptional activation domain, and thus acted as...
