Table 1.
An overview of recent studies investigating chitinases in the context of ALS.
| Study PMID | Study targets | Participants | Sample type | Methods used | Relative expression in ALS* | Correlation with neurofilament levels* | Other targets | Proposed bio mechanism | Proposed utility | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ALS | HCs | Mimics NDegs, NDCs | Other groups | |||||||||
| 31175169 | CHIT1 and CHI3L1 | 105 | 16 mimics, 102 NDCs | CSF and serum | ELISA and chemiluminescent assays | CSF CHIT and CHI3L1 ↑NDCs, Mimics | All with pNfH and NfL (in CSF) | MCP-1 | Surrogate markers of Gliosis | Monitoring therapy response and stratification | ||
| 31123140 | CHIT1, CHI3L1, CHI3L2 | 82 | 25 | 12 mimics, 10 PLS | 5 asym gALS MCs | CSF and serum | ELISA, enzymatic activity assay | CSF All ↑HCs, Mimics, MCs, CSF CHIT, CHI3L2↑PLS | All with pNfH (in CSF) | C-RP | Glial activity | Adjunctive predictor of progression, monitoring glial response to therapy |
| 30224549 | CHIT1 CHI3L1 | 70 sALS, 65 gALS | 36 HCs | 26 sFTD, 23 gFTD | 26 asym. gALS MCs | CSF and blood | ELISA | CSF CHIT↑HCs, MCs, gFTD, Blood CHIT↑HCs, CSF CHI3L1 for gALS, and gFTD↑HCs, MCs | All with pNfH and NfL (in CSF) | GFAP | Microglial activity and astrogliosis. Neuroinflammation is common to gALS and sALS | |
| 30215603 | CHI3L1 | IHC 11, ELISA 86, RT-qPCR 12 all sALS | IHC 23, ELISA 21, RT-qPCR 10 | CSF, blood, spinal cord and frontal cortex PMT | RT-qPCR, IHC, ELISA, IB | PMT CHI3L1, CHI3L1 ↑HCs, CSF CHI3L1↑HCs | NfL | AIF1, CD68, IBA1, GFAP | Increased astroglial activity | Potential prognostic marker when used with NfL | ||
| 29142138 | CHIT1 | ELISA 60, IHC 3 | ELISA 25, IHC 2 | ELISA 46 NDCs and 135 Ndegs, IHC NDegs 4 | CSF, blood, spinal cord PMT | ELISA, IHC | CSF CHIT↑HCs, NDCs, NDegs, Spinal cord PMT CHIT↑NDegs, HCs | pNfH and NfL (in CSF) | IBA1, CD68 | Microglial/macrophage activation | Biomarker for immune activation; can be used to monitor efficacy of immunomodulatory therapies | |
| 29331073 | CHIT1, CHI3L1, CHI3L2 | 43 | 25 | 6 PLS, 12 mimics, 20 NDeg | CSF | High throughput MS, ELISA (for pNfH) | CHIT1, CHI3L2 ↑HCs, Mimics, NDeg, PLS, CHI3L1↑HCs, Mimics, NDeg | All with pNfH | Microglial activity | Distinguishing between ALS and ALS mimic conditions | ||
| 30134252 | CHIT1 | 29 | 36 | CSF and blood | ELISA, chemiluminescence, enzymatic activity assay | CSF CHIT1 activity↑HCs | CCL18, TNF-α, IL6, CHIT1 | Microglial activation | Neuroinflammation biomarker | |||
| 30291183 | CHI3L1 | 38 | 49 | 86 FTD | CSF | ELISA | CHI3L1↑HCs | NfL | sAPPβ | Staging and prognosis along ALS-FTD spectrum | ||
| 25563799 | CHIT1 | 75 | 106 | Blood | Enzymatic activity assay | CHIT1 activity↑HCs | Lysosomal enzyme activity | Microglial activity and possible chronic triggering of the innate immune system | ||||
| 27634542 | CHIT1 | 40 sALS | 40 NDCs | CSF | ELISA | CHIT1↑NDCs | pNfH | S100-β, Cystatin C | Improves diagnostic potential when used with pNfH | |||
| 24295388 | CHIT1, CHI3L1, CHI3L2 | 26 sALS | 23 | CSF | LC-MS/MS, ELISA, enzymatic activity assay | CHIT1, CHI3L2↑HCs, CHIT activity ↑HCs | Osteopontin | Microglial activity and potential response to deposition of chitin-like substances in CNS aggregates | ||||
Reported results were statistically significant.
AIF-1, Allograft inflammatory factor 1; asym, asymptomatic; CCL-18, Chemokine ligand 18; C-RP, C Reactive Protein; CSF, cerebrospinal fluid; ELISA, Enzyme-linked Immunosorbent assay; FTD, frontotemporal dementia; gALS, genetic Amyotrophic Lateral Sclerosis; GFAP, glial fibrillary acidic protein; gFTD, genetic Frontotemporal Dementia; HCs, Healthy Controls; IB, Immunoblotting; IHC, Immunohistochemistry; IL-6, interleukin 6; LC-MS, Liquid Chromatography Mass Spectrometry; MCs, Mutation Carriers; MCP-1, Monocyte chemoattractant protein 1; MS, Mass Spectrometry; NDCs, Neurological Disease Controls; NDegs, Neurodegenerative Disease Controls; NfL, neurofilament light chain; PLS, Primary Lateral Sclerosis; PMT, Post-mortem Tissue; pNfH, phosphorylated neurofilament heavy chain; RT-qPCR, Real-time Quantitative Polymerase Chain Reaction; sALS, sporadic ALS; sAPPβ, soluble amyloid precursor protein beta; sFTD, sporadic Frontotemporal Dementia; TNF-α, tumor necrosis factor alpha.