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

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.

• Publication year

  2017

• Venue

  Acta Neuropathologica Communications

• Publication date

  2017-03-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s40478-017-0420-1PMID 28274274PMCID 5341362
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing

  2016cited by this paper
• Targeting TEAD/YAP-transcription-dependent necrosis, TRIAD, ameliorates Huntington's disease pathology.

  2016cited by this paper
• c-Abl antagonizes the YAP oncogenic function

  2014cited by this paper
• Rapamycin increases survival in ALS mice lacking mature lymphocytes

  2013cited by this paper
• Rapamycin treatment augments motor neuron degeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis

  2011cited by this paper
• Polo-like kinases mediate cell survival in mitochondrial dysfunction

  2009cited by this paper
• Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SOD1 gene

  2009cited by this paper
• Progressive decrease in the level of YAPdeltaCs, prosurvival isoforms of YAP, in the spinal cord of transgenic mouse carrying a mutant SOD1 gene

  2009influential reference
• Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.

  2007cited by this paper
• Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73

  2006cited by this paper
• Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice

  2002cited by this paper
• [Corticobasal degeneration].

  2001cited by this paper
• Fragmentation of the Golgi apparatus of the ballooned neurons in patients with corticobasal degeneration and Creutzfeldt-Jakob disease

  2000cited by this paper
• Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse.

  1999influential reference
• Ballooned neurons in corticobasal degeneration and progressive supranuclear palsy

  1997influential reference
• Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.

  1996cited by this paper
• Ballooned neurons in several neurodegenerative diseases and stroke contain αB crystallin

  1992cited by this paper
• Ballooned neurons in several neurodegenerative diseases and stroke contain alpha B crystallin.

  1992cited by this paper
• Lobar atrophy with pontine neuronal chromatolysis ("ballooned" neurons).

  1990cited by this paper
• Corticobasal degeneration.

  1989cited by this paper
• The morphology of various types of cell death in prenatal tissues.

  1973cited by this paper
• Corticodentatonigral degeneration with neuronal achromasia.

  1968cited by this paper

• The diverse forms and roles of the neuronal endoplasmic reticulum.

  2026cites this paper
• YAP/TAZ in the nervous system: Key regulatory and therapeutic implications in neurological disorders.

  2025cites this paper
• Discovery and Optimization of LATS1 and LATS2 Kinase Inhibitors for Use in Regenerative Medicine

  2025cites this paper
• Neuroprotective role of Hippo signaling by microtubule stability control in Caenorhabditis elegans

  2025cites this paper
• The Hippo signaling pathway as a therapeutic target in Alzheimer’s disease

  2025cites this paper
• Live and let die: analyzing ultrastructural features in cell death

  2024cites this paper
• Neuronal regulated cell death in aging-related neurodegenerative diseases: key pathways and therapeutic potentials

  2024cites this paper
• Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease

  2024influential citation
• Unwinding the modalities of necrosome activation and necroptosis machinery in neurological diseases.

  2023cites this paper
• Emerging Roles of Signal Transduction Pathways in Neurodegenerative Diseases. Hunting New Possible Therapeutic Molecular Targets

  2023cites this paper
• The Complex Mechanisms by Which Neurons Die Following DNA Damage in Neurodegenerative Diseases

  2022cites this paper
• Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington’s Disease and Other Neurodegenerative Disorders

  2022cites this paper
• The Hippo signalling pathway and its implications in human health and diseases

  2022cites this paper
• Temporal Characterization of Behavioral and Hippocampal Dysfunction in the YAC128 Mouse Model of Huntington’s Disease

  2022influential citation
• Oncogenic Pathways in Neurodegenerative Diseases

  2022cites this paper
• Mechanosensing and the Hippo Pathway in Microglia: A Potential Link to Alzheimer’s Disease Pathogenesis?

  2021cites this paper
• Intracellular amyloid hypothesis for ultra‐early phase pathology of Alzheimer's disease

  2021cites this paper
• DNA damage in embryonic neural stem cell determines FTLDs’ fate via early-stage neuronal necrosis

  2021cites this paper
• Polo-like kinase 1 (PLK1) signaling in cancer and beyond.

  2021cites this paper
• Willin/FRMD6: A Multi-Functional Neuronal Protein Associated with Alzheimer’s Disease

  2021cites this paper
• Non-Cell Autonomous and Epigenetic Mechanisms of Huntington’s Disease

  2021cites this paper
• Myelinosome Organelles in the Retina of R6/1 Huntington Disease (HD) Mice: Ubiquitous Distribution and Possible Role in Disease Spreading

  2021cites this paper
• YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology

  2020cites this paper
• Pathophysiology of Neuronal Cell Death After Stroke

  2020cites this paper
• Hippo signaling: bridging the gap between cancer and neurodegenerative disorders

  2020influential citation
• Stroke Revisited: Pathophysiology of Stroke: From Bench to Bedside

  2020cites this paper
• Pathology, Prevention and Therapeutics of Neurodegenerative Disease

  2019cites this paper
• The emerging role of Hippo signaling in neurodegeneration

  2019cites this paper
• Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice

  2019cites this paper
• Pathophysiological Mechanisms of Huntington’s Disease

  2018cites this paper
• Amot regulates neuronal dendritic tree through Yap1

  2018cites this paper
• A Network Pharmacology-Based Approach to Investigate the Novel TCM Formula against Huntington's Disease and Validated by Support Vector Machine Model

  2018influential citation
• Hippo Signaling Pathway Dysregulation in Human Huntington’s Disease Brain and Neuronal Stem Cells

  2018cites this paper
• PQBP1, an intrinsically disordered/denatured protein at the crossroad of intellectual disability and neurodegenerative diseases

  2017cites this paper
• Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1

  2017cites this paper