Acta Neuropathologica Communications · 2017 · 43 citations · 18 references
Life SciencesMolecular BiologyNeuroscienceMolecular NeurobiologyMolecular NeuroscienceNeurodegenerationCell DeathHuntington DiseaseNecrosisNeurodegenerative DiseasesNeurodegenerative DisordersNeuronal Cell DeathCell Death In NeurodegenerationHippo SignalingHippo Signaling PathwayNeuronal NecrosisPostmortem NeuropathologyProtein Expression LevelsTranscriptional RepressionTranscriptional Repression Mechanisms
We previously reported transcriptional repression-induced atypical cell death of neuron (TRIAD), a new type of necrosis that is mainly regulated by Hippo pathway signaling and distinct from necroptosis regulated by RIP1/3 pathway. Here, we examined the ultrastructural and biochemical features of neuronal cell death in the brains of human HD patients in parallel with the similar analyses using mutant Htt-knock-in (Htt-KI) mice. LATS1 kinase, the critical regulator and marker of TRIAD, is actually activated in cortical neurons of postmortem human HD and of Htt-KI mouse brains, while apoptosis promoter kinase Plk1 was inactivated in human HD brains. Expression levels of YAP/YAPdeltaC were decreased in cortical neurons of human HD brains. Ultra-structural analyses revealed extreme enlargement of endoplasmic reticulum (ER), which characterizes TRIAD, in cortical neurons of human HD and those of Htt-KI mice. These biochemical and morphological results support that TRIAD occurs in human and mouse neurons under the HD pathology.
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The morphology of various types of cell death in prenatal tissues
J.U. Schweichel, H. J. Merker · Teratology · 1973 · 722 citations