ArticleMolecular neurodegeneration2011
Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 73 citations in OpenAlex.
- Targeting Cathepsins in Neurodegeneration: Biochemical Advances.Biomedicines · 2025Review
- Multiomics approach identifies SERPINB1 as candidate biomarker for spinocerebellar ataxia type 2.Scientific reports · 2025Article
- Cathepsins in Neurological Diseases.International journal of molecular sciences · 2025Review
- A lysosomal surveillance response to stress extends healthspan.Nature cell biology · 2025Article
- The therapeutic potential of (R)-carvedilol in Huntington's disease through enhancement of autophagy-lysosomal pathway via GSK-3β inhibition.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Enhancement of lysosome biogenesis as a potential therapeutic approach for neurodegenerative diseases.Neural regeneration research · 2023Article
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models.Translational neurodegeneration · 2023Article
- Novel Lysosome-Targeting Fluorescence Off-On Photosensitizer for Near-Infrared Hypoxia Imaging and Photodynamic Therapy In Vitro and In Vivo.Molecules (Basel, Switzerland) · 2022Article
- Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models.Autophagy · 2022Article
- Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cerebrospinal fluid biomarkers for assessing Huntington disease onset and severity.Brain communications · 2022Article
- Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington's disease.Stem cell research & therapy · 2021Article
- Inhibition of p38 Mitogen-Activated Protein Kinase Ameliorates HAP40 Depletion-Induced Toxicity and Proteasomal Defect in Huntington's Disease Model.Molecular neurobiology · 2021Article
- Lysosomal Stress Response (LSR): Physiological Importance and Pathological Relevance.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Cathepsins in neuronal plasticity.Neural regeneration research · 2021Article
- N-acetyl-D-glucosamine kinase binds dynein light chain roadblock 1 and promotes protein aggregate clearance.Cell death & disease · 2020Article
- Cerebrospinal fluid endo-lysosomal proteins as potential biomarkers for Huntington's disease.PloS one · 2020Article
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
- Cathepsin B: A sellsword of cancer progression.Cancer letters · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHuntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, macroautophagy initiation has been shown to be highly efficient in neurons whereas lysosomal activities are rate limiting. The role of the lysosomal and other proteases in Huntington is not clear. Some studies suggest that certain protease activities may contribute to toxicity whereas others are consistent with protection. These discrepancies may be due to a number of mechanisms including distinct effects of the specific intermediate digestion products of mutant huntingtin generated by different proteases. These observations suggested a critical need to investigate the consequence of upregulation of individual lysosomal enzyme in mutant huntingtin accumulation and toxicity.
resultsIn this study, we used molecular approaches to enhance lysosomal protease activities and examined their effects on mutant huntingtin level and toxicity. We found that enhanced expression of lysosomal cathepsins D and B resulted in their increased enzymatic activities and reduced both full-length and fragmented huntingtin in transfected HEK cells. Furthermore, enhanced expression of cathepsin D or B protected against mutant huntingtin toxicity in primary neurons, and their neuroprotection is dependent on macroautophagy.
conclusionsThese observations demonstrate a neuroprotective effect of enhancing lysosomal cathepsins in reducing mutant huntingtin level and toxicity in transfected cells. They highlight the potential importance of neuroprotection mediated by cathepsin D or B through macroautophagy.
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Registered trials
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