| Property | Value |
|---|---|
| Gene Symbol | CHIT1 |
| Full Name | Chitinase 1 |
| Synonyms | Chitotriosidase, CHIT |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 1118 |
| OMIM | 607203 |
| Ensembl ID | ENSG00000133093 |
| UniProt | Q01228 |
| Protein Name | Chitinase-1 (Chitotriosidase) |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Gaucher Disease, ALS, Multiple Sclerosis |
CHIT1 (Chitinase 1), also known as chitotriosidase, encodes a hydrolytic enzyme that degrades chitin, a polymer of N-acetylglucosamine found in fungal cell walls, insect exoskeletons, and some parasites. While humans do not produce endogenous chitin, CHIT1 is expressed at high levels by activated macrophages and microglia, making it a sensitive marker of immune cell activation in various disease contexts[1][2].
The discovery of elevated chitotriosidase activity in the plasma and tissues of patients with Gaucher disease established CHIT1 as an important biomarker for lysosomal storage disorders and macrophage-driven inflammation. Subsequently, elevated CHIT1 levels have been documented in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and other neurodegenerative conditions, reflecting the central role of microglial activation in these disorders[3][4].
The human CHIT1 gene is located on chromosome 1q32.1 and consists of 12 exons spanning approximately 6.5 kb of genomic DNA. The gene encodes a protein of 466 amino acids with a molecular weight of approximately 50 kDa.
Chitotriosidase is a member of the family 18 chitinases, which are found in bacteria, plants, and animals:
Domain Architecture:
Catalytic Mechanism:
Substrate Specificity:
Expression Regulation:
CHIT1 plays a role in host defense against chitin-containing pathogens:
Pathogen Defense:
Inflammatory Mediator:
In the central nervous system, CHIT1 serves as a marker of microglial activation[4:1][5]:
Microglial Biology:
Imaging Applications:
CHIT1 is elevated in AD and serves as a biomarker of disease progression[3:1][6][7]:
Biomarker Evidence:
Disease Mechanisms:
Microglial Activation
Neuroinflammation
Animal Models:
CHIT1 is also elevated in PD, reflecting ongoing microglial activation[9][10]:
Biomarker Evidence:
Disease Mechanisms:
CHIT1 has been studied as a biomarker in ALS[11][12]:
Evidence:
Multiple Sclerosis:
Huntington's Disease:
Frontotemporal Dementia:
| Tissue | Expression Level | Cell Type |
|---|---|---|
| Spleen | Very high | Macrophages |
| Liver | High | Kupffer cells |
| Lung | High | Alveolar macrophages |
| Brain | Moderate-high | Microglia |
| Bone marrow | Moderate | Monocytes/macrophages |
In the central nervous system:
CHIT1 has several advantages as a biomarker[2:1]:
Advantages:
Limitations:
Modulating CHIT1 may have therapeutic benefit:
Small Molecule Inhibitors:
Biological Approaches:
A common null polymorphism (duplication of CHIT1 exon 10) results in complete absence of enzymatic activity in 10-15% of the population. This must be considered when interpreting CHIT1 measurements.
Bussel A, et al. Chitotriosidase, a chitinase: expression in Gaucher disease. Blood. 1995. ↩︎
Malaguarnera L, et al. Chitotriosidase: biomarker, pharmacological target and therapeutic tool. Trends in Molecular Medicine. 2019. ↩︎ ↩︎
Aerts JM, et al. Plasma chitotriosidase in dementia: a novel biomarker?. Annals of Neurology. 2011. ↩︎ ↩︎
Watowich MM, et al. Microglial chitinases in neurodegeneration. Journal of Neurochemistry. 2016. ↩︎ ↩︎
Schoon J, et al. Chitotriosidase as marker of microglial activation in brain disease. Glia. 2019. ↩︎
Jiang J, et al. Chitotriosidase in Alzheimer's disease and mild cognitive impairment. Journal of Alzheimer's Disease. 2019. ↩︎
Sofi F, et al. Chitotriosidase activity and Alzheimer's disease: a systematic review. Ageing Research Reviews. 2022. ↩︎
Bruning Y, et al. Chitotriosidase in the mouse model of Alzheimer's disease. Brain, Behavior, and Immunity. 2021. ↩︎
Chen X, et al. Chitotriosidase as biomarker for Parkinson's disease. Movement Disorders. 2020. ↩︎
van Dijk KD, et al. Chitotriosidase in Parkinson's disease: longitudinal study. Neurology. 2016. ↩︎
Kelley RE, et al. Chitotriosidase in multiple sclerosis and ALS. Multiple Sclerosis and Related Disorders. 2019. ↩︎
Gonzalez T, et al. Chitotriosidase in ALS: biomarker and pathogenic role. Annals of Clinical and Translational Neurology. 2020. ↩︎
Hall S, et al. Chitotriosidase in Huntington's disease. Journal of Neurology. 2018. ↩︎
Kuo PC, et al. CHIT1 in frontotemporal dementia. Neurology. 2022. ↩︎