ArticleNature communications2024
HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Chaperone-mediated remodelling of mutant huntingtin.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Genetic architecture and molecular pathogenesis of Parkinson's disease: emerging mechanisms and therapeutic targets.Metabolic brain disease · 2026Review
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The expanding role of protease therapeutics (2012-2026): from replacement therapies to immune system modulation and beyond.The Biochemical journal · 2026Review
- High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Molecular cell · 2026Article
- The Amyloid Plaque Proteomes of Alzheimer's Disease and Mild Cognitive Impairment.Research square · 2026Article
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- Single Plaque Proteomics Reveals the Composition and Dynamics of the Amyloid Microenvironment in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Rare Variants in HTRA1, SGTB, and RBM12 Confer Risk of Atherosclerotic Cardiovascular Disease Independent of Traditional Cardiovascular Risk Factors.Circulation. Genomic and precision medicine · 2025Article
- Matrin-3 forms spherical and wormlike assemblies that are modulated by RNA binding and ALS/FTD-associated mutations.Molecular cell · 2025Article
- Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide.NPJ Parkinson's disease · 2025Article
- Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface.ACS chemical biology · 2025Article
- Defined human tri-lineage brain microtissues.bioRxiv : the preprint server for biology · 2025Article
- Proteomic landscape of Alzheimer's disease: emerging technologies, advances and insights (2021 - 2025).Molecular neurodegeneration · 2025Review
- Human and mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome.Nature communications · 2025Article
- Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.Nature communications · 2025Article
- Seeding-competent TDP-43 persists in human patient and mouse muscle.Science translational medicine · 2024Article
- Human-mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome.bioRxiv : the preprint server for biology · 2024Article
- Seeding competent TDP-43 persists in human patient and mouse muscle.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Parkinson's disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which is associated with Alzheimer's disease, and inactivating mutations to mitochondrial HTRA2 are implicated in PD. Here, we report that HTRA1 inhibits aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The protease domain of HTRA1 is necessary and sufficient for inhibiting aggregation, yet this activity is proteolytically-independent. Further, HTRA1 disaggregates preformed α-syn fibrils, rendering them incapable of seeding aggregation of endogenous α-syn, while reducing HTRA1 expression promotes α-syn seeding. HTRA1 remodels α-syn fibrils by targeting the NAC domain, the key domain catalyzing α-syn amyloidogenesis. Finally, HTRA1 detoxifies α-syn fibrils and prevents formation of hyperphosphorylated α-syn accumulations in primary neurons. Our findings suggest that HTRA1 may be a therapeutic target for a range of neurodegenerative disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.