ArticleThe Journal of biological chemistry2012
Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 96 citations in OpenAlex.
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Extracellular Protein Quality Control in Tau Pathology.Molecular neurobiology · 2026Review
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Assessing Aβ-independent effects of Module 42 on immune function in vitro.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- HTRA1 and complement activation in neovascular age-related macular degeneration.Japanese journal of ophthalmology · 2025Article
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Immune Responses Elicited by Outer Membrane Vesicles of Gram-Negative Bacteria: Important Players in Vaccine Development.Life (Basel, Switzerland) · 2024Review
- Rapid prediction of key residues for foldability by machine learning model enables the design of highly functional libraries with hyperstable constrained peptide scaffolds.PLoS computational biology · 2024Article
- Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.Nature communications · 2024Article
- TYROBP/DAP12 knockout in Huntington's disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration.Journal of neuroinflammation · 2024Article
- Article
- Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023Review
- The emerging role of the HTRA1 protease in brain microvascular disease.Frontiers in dementia · 2023Review
- Reversible protein assemblies in the proteostasis network in health and disease.Frontiers in molecular biosciences · 2023Review
- HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case-control study and a prospective nested case-control study.Clinical epigenetics · 2022Article
- Report of two pedigrees with heterozygous HTRA1 variants-related cerebral small vessel disease and literature review.Molecular genetics & genomic medicine · 2022Review
- Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.Molecular psychiatry · 2022Review
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
- Structural basis of protein substrate processing by human mitochondrial high-temperature requirement A2 protease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control. So far, however, no HtrA protease is known that degrades protein aggregates. We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations. These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed.
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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.