Target intelligence / Profile preview

Aggrecan and other hyaluronan-binding extracellular matrix proteoglycans (Hyalectans) (Hyalectans)

Target
Hyalectans
Molecular classification
Extracellular matrix protein, Proteoglycan, Hyaluronan-binding protein, Lectican
01

Overview

Aggrecan and other hyaluronan-binding extracellular matrix proteoglycans, collectively known as hyalectans or lecticans, are critical structural components of the extracellular matrix (ECM). This family includes aggrecan, versican, neurocan, and brevican, which are characterized by an N-terminal hyaluronan-binding domain and a C-terminal lectin-like domain (UniProt P16112; PMID: 10842358). Aggrecan is the most abundant proteoglycan in cartilage, providing the osmotic swelling pressure necessary for load-bearing and shock absorption (PMID: 24075861). In disease states like osteoarthritis and intervertebral disc degeneration, the proteolytic cleavage of these proteoglycans by enzymes such as ADAMTS-4 and ADAMTS-5 leads to matrix depletion and functional loss (PMID: 18220414). Therapeutic strategies often focus on inhibiting these degradative enzymes or replenishing the ECM components to restore tissue integrity. Additionally, these proteoglycans play significant roles in the central nervous system, where they contribute to the perineuronal nets that regulate synaptic plasticity and inhibit axonal regeneration after injury (PMID: 11030571).

Other names
LecticansHyaluronan-binding proteoglycansLarge aggregating proteoglycansChondroitin sulfate proteoglycansACANVCANNCANBCAN
02

Mechanism of action

Inhibition of proteolytic degradation by aggrecanases (ADAMTS) and matrix metalloproteinases (MMPs), or supplementation of matrix components to restore structural integrity.

03

Biological functions

Extracellular matrix organizationCell adhesionCell migrationStructural supportHydrationNeural plasticity
04

Disease associations

OsteoarthritisIntervertebral disc degenerationCancerCentral nervous system injurySkeletal dysplasia
05

Safety considerations

Off-target effects in non-target connective tissuesPotential interference with normal CNS plasticityDifficulty in drug delivery to avascular tissues like cartilage
06

Interacting drugs

Pentosan polysulfate

5 more in the full profile.

07

Biomarkers

ARGS neoepitopeKeratan sulfateChondroitin sulfateAggrecan fragments

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