ArticleJournal of neuroinflammation2020
Chitotriosidase, a biomarker of amyotrophic lateral sclerosis, accentuates neurodegeneration in spinal motor neurons through neuroinflammation.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Pooled it
- Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Inflammatory checkpoints in amyotrophic lateral sclerosis: From biomarkers to therapeutic targets.Frontiers in immunology · 2022Pooled it
- Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial.Cell transplantationTrial
- Constitutive neuronal expression and disease-associated upregulation of chitinases in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- Metabolic and Fluid Biomarkers Support Microglia Activation in Amyotrophic Lateral Sclerosis.Annals of clinical and translational neurology · 2026Article
- Cerebrospinal Fluid From Patients With HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) With Rapid Evolution Affects Mitochondrial DNA Transcription and Network Organization in Human Glioblastoma Cells.Journal of medical virology · 2025Article
- Human chitinases and chitinase-like proteins as emerging drug targets - a medicinal chemistry perspective.RSC medicinal chemistry · 2025Review
- Review
- A field resource for the glioma cerebrospinal fluid proteome: Impacts of resection and location on biomarker discovery.Neuro-oncology · 2025Article
- Transkingdom mechanism of MAMP generation by chitotriosidase feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing.Frontiers in immunology · 2025Article
- Article
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.medRxiv : the preprint server for health sciences · 2024Article
- Follow-up of pre-motor symptoms of Parkinson's disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF.Orphanet journal of rare diseases · 2023Article
- Plasma CHI3L1 in Amyotrophic Lateral Sclerosis: A Potential Differential Diagnostic Biomarker.Journal of clinical medicine · 2023Article
- Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis.European journal of neurology · 2022Observational
- Cerebrospinal fluid biomarkers of disease activity and progression in amyotrophic lateral sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2022Review
- Chitotriosidase 1 in the cerebrospinal fluid as a putative biomarker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) progression.Frontiers in immunology · 2022Article
- Apolipoprotein B-100-mediated motor neuron degeneration in sporadic amyotrophic lateral sclerosis.Brain communications · 2022Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCerebrospinal fluid from amyotrophic lateral sclerosis patients (ALS-CSF) induces neurodegenerative changes in motor neurons and gliosis in sporadic ALS models. Search for identification of toxic factor(s) in CSF revealed an enhancement in the level and enzyme activity of chitotriosidase (CHIT-1). Here, we have investigated its upregulation in a large cohort of samples and more importantly its role in ALS pathogenesis in a rat model.
methodsCHIT-1 level in CSF samples from ALS (n = 158), non-ALS (n = 12) and normal (n = 48) subjects were measured using ELISA. Enzyme activity was also assessed (ALS, n = 56; non-ALS, n = 10 and normal-CSF, n = 45). Recombinant CHIT-1 was intrathecally injected into Wistar rat neonates. Lumbar spinal cord sections were stained for Iba1, glial fibrillary acidic protein and choline acetyl transferase to identify microglia, astrocytes and motor neurons respectively after 48 h of injection. Levels of tumour necrosis factor-α and interleukin-6 were measured by ELISA.
findingsCHIT-1 level in ALS-CSF samples was increased by 20-fold and it can distinguish ALS patients with a sensitivity of 87% and specificity of 83.3% at a cut off level of 1405.43 pg/ml. Enzyme activity of CHIT-1 was also 15-fold higher in ALS-CSF and has a sensitivity of 80.4% and specificity of 80% at cut off value of 0.1077989 μmol/μl/min. Combining CHIT-1 level and activity together gave a positive predictive value of 97.78% and negative predictive value of 100%. Administration of CHIT-1 increased microglial numbers and astrogliosis in the ventral horn with a concomitant increase in the levels of pro-inflammatory cytokines. Amoeboid-shaped microglial and astroglial cells were also present around the central canal. CHIT-1 administration also resulted in the reduction of motor neurons.
conclusionsCHIT-1, an early diagnostic biomarker of sporadic ALS, activates glia priming them to attain a toxic phenotype resulting in neuroinflammation leading to motor neuronal death.
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