Chitinases and chitinase-like proteins as biomarkers in neurologic disorders

Pinteac, Rucsanda; Montalbán, Xavier; Comabella, Manuel

doi:10.1212/nxi.0000000000000921

Cited by 53 publications

(76 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with our finding of CHIT1 being negatively correlated with the MoCA scores, chitinases including CHIT1 have emerged as biomarkers in neurological disorders as their levels correlate with disease activity and progression, likely reflecting microglia/macrophage activation [83,84]. In addition, levels of proteins such as CHS T6 correlate well with disease progression, as measured by the UPDRS (Figures 6A and S4).…”

Section: Discussionsupporting

confidence: 82%

Proteome Profiling of Cerebrospinal Fluid Reveals Novel Biomarker Candidates for Parkinson’s Disease

Karayel

Winter

Padmanabhan

et al. 2021

Preprint

View full text Add to dashboard Cite

Parkinson's disease (PD) is a growing burden worldwide, and despite ongoing efforts to find reliable biomarkers for early and differential diagnosis, prognosis and disease monitoring, there is no biofluid biomarker used in clinical routine to date. Cerebrospinal fluid (CSF) is collected often and should closely reflect structural and functional alterations in PD patients' brains. Here we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling to find specific biomarkers and identify disease-related changes in CSF protein levels in PD. From two independent cohorts consisting of more than 200 individuals, our workflow reproducibly quantified over 1,700 proteins from minimal sample amounts. Combined with machine learning, this identified a group of several proteins, including OMD, CD44, VGF, PRL, and MAN2B1 that were altered in PD patients or significantly correlate with clinical scores, indicative of disease progression. Interestingly, we uncovered signatures of enhanced neuroinflammation in patients with familial PD (LRRK2 G2019S carriers) as indicated by increased levels of CTSS, PLD4, HLA-DRA, HLA-DRB1, and HLA-DPA1. A comparison with urinary proteome changes in PD patients revealed a large overlap in protein composition PD-associated changes in these body fluids, including lysosomal factors like CTSS. Our results validate MS-based proteomics of CSF as a valuable strategy for biomarker discovery and patient stratification in a neurodegenerative disease like PD. Consistent proteomic signatures across two independent CSF cohorts and previously acquired urinary proteome profiles open up new avenues to improve our understanding of PD pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 82%

Proteome Profiling of Cerebrospinal Fluid Reveals Novel Biomarker Candidates for Parkinson’s Disease

Karayel

Winter

Padmanabhan

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Unfortunately, NF are also increased in other neurological diseases, driving the need to find additional targets. The value of chitinases as biomarkers for amyotrophic lateral sclerosis has been supported by strong recent evidence [ 12 , 26 , 27 ]. CHIT1 has been advanced as an ALS biomarker in diagnosis and progression [ 13 , 16 , 28 , 29 , 30 , 31 ], as has CHI3L1 [ 16 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 98%

“…Although mammals do not contain endogenous chitin or chitin synthases genes, several cells in the human body, including activated immune cells, are capable of producing chitinases [ 12 ]. Chitinases in mammals belong to the glycoside hydrolase 18 family (CAZy, GH18).…”

Section: Introductionmentioning

confidence: 99%

“…CHIT1 (EC 3.2.1.14) cleaves glycosidic linkages in chitin, which is a linear polymer of β1,4 linked N-acetylglucosamine (GlcNAc). CHIT1 was detected in microglia from the corticospinal tract [ 13 ] in macrophages and neutrophils [ 12 ]. Chitin-like proteins include CHI3L1 (YKL-40) and CHI3L2 (YKL-39) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…CHI3L1 was found to bind heparin and play a role in cell signaling [ 15 ]. CHI3L1 was detected in a subset of activated astrocytes in the white matter of the motor cortex and spinal cord of ALS patients [ 16 ], as well as in monocytes/macrophages, chondrocytes, synovial cells and osteoclasts [ 12 ]. CHI3L2 has been detected in macrophages, tumor cells [ 17 ] and cartilage chondrocytes [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

et al. 2021

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

show abstract

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Lathe

Schultek²,

Balin

et al. 2023

Alzheimer's & Dementia

View full text Add to dashboard Cite

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

show abstract

Chitinases and chitinase-like proteins as biomarkers in neurologic disorders

Cited by 53 publications

References 68 publications

Proteome Profiling of Cerebrospinal Fluid Reveals Novel Biomarker Candidates for Parkinson’s Disease

Proteome Profiling of Cerebrospinal Fluid Reveals Novel Biomarker Candidates for Parkinson’s Disease

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Contact Info

Product

Resources

About