ArticleMolecular and cellular neurosciences2018
Aberrant subcellular localization of SQSTM1/p62 contributes to increased vulnerability to proteotoxic stress recovery in Huntington's disease.
Article in Molecular and cellular neurosciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.International journal of molecular sciences · 2024Review
- Article
- Bafilomycin 1A Affects p62/SQSTM1 Autophagy Marker Protein Level and Autophagosome Puncta Formation Oppositely under Various Inflammatory Conditions in Cultured Rat Microglial Cells.International journal of molecular sciences · 2024Article
- Proteasomal inhibition preferentially stimulates lysosome activity relative to autophagic flux in primary astrocytes.Autophagy · 2023Article
- Characterization of huntingtin interactomes and their dynamic responses in living cells by proximity proteomics.Journal of neurochemistry · 2023Article
- LAFITE Reveals the Complexity of Transcript Isoforms in Subcellular Fractions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Impaired Restoration of Global Protein Synthesis Contributes to Increased Vulnerability to Acute ER Stress Recovery in Huntington's Disease.Cellular and molecular neurobiology · 2022Article
- Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging.Frontiers in cell and developmental biology · 2022Review
- Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions.Biomedicines · 2021Review
- The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin.Molecules (Basel, Switzerland) · 2021Review
- RNA-seq analysis reveals significant transcriptome changes in huntingtin-null human neuroblastoma cells.BMC medical genomics · 2021Article
- The therapeutic effect of TBK1 in intervertebral disc degeneration via coordinating selective autophagy and autophagic functions.Journal of advanced research · 2021Article
- How Do Post-Translational Modifications Influence the Pathomechanistic Landscape of Huntington's Disease? A Comprehensive Review.International journal of molecular sciences · 2020Review
- Case report and literature review of Huntington disease with intermediate CAG expansion.BMJ neurology open · 2020Article
- SQSTM1/p62: A Potential Target for Neurodegenerative Disease.ACS chemical neuroscience · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
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Abstract
Proteotoxic stress plays an important role in the pathogenesis of Huntington's disease (HD). Autophagy is proposed as a compensatory mechanism to remove protein aggregates under proteotoxic stress by up-regulating p62 expression. In the present study, we investigated the molecular action of p62 to proteotoxic stress in HD cells. Using two different HD cellular models, STHdhQ7 and STHdhQ111 cells derived from wild type and HD knock-in mice and human fibroblasts from healthy and HD patients, we found that HD cells are more vulnerable to cell death under proteotoxic stress and during stress recovery. We further showed that P62 was up-regulated in both STHdhQ7 and STHdhQ111 cells in response to the stress with distinct subcellular localization patterns. While dispersed p62 puncti were found in STHdhQ7 cells, p62 bodies were initially present in the lysosomes and accumulated to the juxtanuclear regions of STHdhQ111 cells as MG132 incubation continued. Unlike in STHdhQ7 cells, p62 puncti were not associated with K48-linked polyubiquitinated protein aggregates or proteasomal components in STHdhQ111. Interestingly, addition of cysteine during MG132 incubation rescued cell death in STHdhQ111 cells caused by stress recovery and altered the subcellular distribution of p62. Our data suggest that aberrant positioning of p62 affects the proteasomal clearance of protein aggregates and may contribute to the increased vulnerability to proteotoxic stress-induced cell death in HD cells.
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