A novel form of necrosis, TRIAD, occurs in human Huntington's disease

作者：Yamanishi Emiko; Hasegawa Kazuko; Fujita Kyota; Ichinose Shizuko; Yagishita Saburo; Murata Miho; Tagawa Kazuhiko; Akashi Takumi; Eishi Yoshinobu; Okazawa Hitoshi^*

来源：Acta Neuropathologica Communications, 2017, 5(1): 19.

DOI：10.1186/s40478-017-0420-1

• TRIAD
• Necrosis
• Huntington's disease
• LATS
• Neurodegeneration
• TEAD
• YAP
• Hippo pathway
• Electron microscopy

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.

• 出版日期2017-3-8