YKL-40 and LAMPs as possible markers in neuroinflammation and autophagy during central nervous system infections

Figures & data

Table 1. Basic characteristics of YKL-40, LAMP-1 and LAMP-2.

Name	Gene symbol, chromosome localization	Protein structure, interaction, amino acids	Biological function	Cellular source in healthy conditions	Subcellular location	Signaling pathways
YKL-40	CHI3L1, chromosome 1; 10 exons	383 AA, monomer	Tissue remodeling and angiogenesis; induced Th2 inflammatory response and M2 macrophage differentiation; modulates antibacterial responses [10,12,29]	Expressed by monocytes/macrophages, chondrocytes, synovial cells, osteoclasts, and microglia [30,31].	Cytoplasmic granular [32]	Activates the Erk, Akt, and Wnt-linked signaling pathways [33,34]
LAMP-1	LAMP1, chromosome 13	417 AA, Homodimer	Lysosome biogenesis, autophagy, and cholesterol homeostasis; NK-cells cytotoxicity [35]; Cytotoxic granule movement to the cell surface and perforin trafficking to the lytic granule [36]. NK-cells are protected by degranulation [37]. Presents carbohydrate ligands to selectins. Implicated in tumor cell metastasis.	Distributed among autophagic and endolysosomal organelles [28]	Endosome-lysosomal membrane of cells and plasma membrane [38]	Participates in endocytic and autophagic pathways and lysosomal biogenesis [39]
LAMP-2	LAMP2, chromosome X	410 AA, monomer, homodimer	Chaperone-mediated autophagy, supports the FURIN-mediated cleavage of mumps virus fusion protein F (P13473) [40]	Distributed among autophagic and endolysosomal organelles [41].	Endosome-lysosomal membrane of cells and plasma membrane [38]	Mediates response to elevated platelet cytosolic Ca2+ and innate immune response

Figure 1. Interplay between autophagy and inflammation.

Table 2. Summary of YKL-40, LAMPs studies in CNS infections.

	Markers
Disease	YKL-40	LAMP-1 and LAMP-2
Anti-leucine-rich glioma inactivated 1(LGI1) encephalitis	CHI3L1 levels in CSF and serum are highly elevated compared to controls. CSF CHI3L1 levels are correlated with the severity and prognosis of LGI1 [22]	N/D
Tick-borne encephalitis: meningoencephalitis and meningitis [23]	The concentration is significantly elevated in the group than the controls the after 7 days from the last dose of treatment.	Autophagy restricts the replication of several viruses in neurons [21]
N-methyl-D-aspartate receptor encephalitis	CSF levels of YKL-40 and inflammatory cytokines (TNF-a, IL-6, IL-10) are all higher in patients with anti-NMDAR encephalitis at the acute stage of disease compared with the controls [21]	N/D
Creutzfeldt–Jakob (CJD) disease	Concentrations are elevated in patients with CJD vs patients with Alzheimer’s disease, frontotemporal dementia and controls (CSF) [57] Levels are elevated in patients with CJD vs patients with neurodegenerative disorders, neurologic controls, and healthy individuals [58]	N/D
HIV-1 infections, Herpes simplex virus type 1 (HSV1)	CSF YKL-40 is a candidate biomarker for understanding the pathogenesis of HIV in the CNS. Strong correlation between CSF YKL-40 and NFL indicates a pathogenic association between astroglial activation and axonal injury [59]	HIV infection induces damage-regulated autophagy modulator (DRAM) expression in a p53-dependent manner [60] LAMP-2 deficiency affects more severely the lysosomal dysfunction induced by HSV 1 infection [43]

Note: N/D – not determined.

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Data availability statement

Data is available from the corresponding author upon request.