Last update 01 Nov 2024

CSPG4 x Chondroitin sulfate proteoglycans

Last update 01 Nov 2024

Basic Info

Related Targets

CSPG4Chondroitin sulfate proteoglycans

Drugs associated with CSPG4 x Chondroitin sulfate proteoglycans

M4-3-ML2

Target

CSPG4 x Chondroitin sulfate proteoglycans

Mechanism

CSPG4 gene modulators [+1]

Active Org.

Roche Holding AG

Originator Org.

Roche Holding AG

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CSPG4 x Chondroitin sulfate proteoglycans

100 Translational Medicine associated with CSPG4 x Chondroitin sulfate proteoglycans

0 Patents (Medical) associated with CSPG4 x Chondroitin sulfate proteoglycans

Literatures (Medical) associated with CSPG4 x Chondroitin sulfate proteoglycans

01 Sep 2021·Molecular NeurobiologyQ2 · MEDICINE

Neutrophil, Extracellular Matrix Components, and Their Interlinked Action in Promoting Secondary Pathogenesis After Spinal Cord Injury

Q2 · MEDICINE

Review

Author: Kumar, Hemant ; Dolma, Sonam

Secondary pathogenesis following primary mechanical damage to the spinal cord is believed to be the ultimate reason for the limitation of currently available therapies. Precisely, the complex cascade of secondary events-mediated scar formation is the sole hurdle in the recovery process due to its inhibitory effect on axonal regeneration, plasticity, and remyelination. Neutrophils initiate this secondary injury along with other extracellular matrix components such as matrix metalloproteinase (MMPs), and chondroitin sulfate proteoglycans (CSPGs). Together, they mediate inflammation, necrosis, apoptosis, lesion, and scar formation at the injury site. Activated neutrophil releases several proteases, cytokines, and chemokines that cause complete tissue destruction. Thus, neutrophil activation and infiltration in the acute phase of injury act as a roadmap for inducing tissue destruction. MMPs, are extracellular proteolytic enzymes that degrade the ECM proteins, increases vascular permeability, and are predominantly released by neutrophils. These MMPs, in turn, cleave NG2 proteoglycan, a subtype of CSPG, into the active form. This active or shed form is involved in both the fibrotic as well as glial scar formation. Since neutrophils and ECM components are closely associated with each other in pathological conditions. Herein, we emphasize the interaction of neutrophils and their influence on ECM protein expression during the acute and chronic phases to identify a promising targets for designing a therapeutic approach in spinal cord injury.

16 Jun 2020·Oncotarget

Increased CHST15 follows decline in arylsulfatase B (ARSB) and disinhibition of non-canonical WNT signaling: potential impact on epithelial and mesenchymal identity

Article

Author: Feferman, Leo ; Zhang, Fuming ; Bhattacharyya, Sumit ; Tobacman, Joanne K. ; Linhardt, Robert J. ; Xia, Ke ; Han, Xiaorui

Expression of CHST15 (carbohydrate sulfotransferase 15; chondroitin 4-sulfate-6-sulfotransferase; BRAG), the sulfotransferase enzyme that adds 6-sulfate to chondroitin 4-sulfate (C4S) to make chondroitin 4,6-disulfate (chondroitin sulfate E, CSE), was increased in malignant prostate epithelium obtained by laser capture microdissection and following arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) silencing in human prostate epithelial cells. Experiments in normal and malignant human prostate epithelial and stromal cells and tissues, in HepG2 cells, and in the ARSB-null mouse were performed to determine the pathway by which CHST15 expression is up-regulated when ARSB expression is reduced. Effects of Wnt-containing prostate stromal cell spent media and selective inhibitors of WNT, JNK, p38, SHP2, β-catenin, Rho, and Rac-1 signaling pathways were determined. Activation of WNT signaling followed declines in ARSB and Dickkopf WNT Signaling Pathway Inhibitor (DKK)3 and was required for increased CHST15 expression. The increase in expression of CHST15 followed activation of non-canonical WNT signaling and involved Wnt3A, Rac-1 GTPase, phospho-p38 MAPK, and nuclear DNA-bound GATA-3. Inhibition of JNK, Sp1, β-catenin nuclear translocation, or Rho kinase had no effect. Consistent with higher expression of CHST15 in prostate epithelium, disaccharide analysis showed higher levels of CSE and chondroitin 6-sulfate (C6S) disaccharides in prostate epithelial cells. In contrast, chondroitin 4-sulfate (C4S) disaccharides were greater in prostate stromal cells. CSE may contribute to increased C4S in malignant epithelium when GALNS (N-aceytylgalactosamine-6-sulfate sulfatase) is increased and ARSB is reduced. These effects increase chondroitin 4-sulfates and reduce chondroitin 6-sulfates, consistent with enhanced stromal characteristics and epithelial-mesenchymal transition.

01 Jun 2020·GliaQ1 · MEDICINE

2‐arachidonoylglycerol reduces chondroitin sulphate proteoglycan production by astrocytes and enhances oligodendrocyte differentiation under inhibitory conditions

Q1 · MEDICINE

Article

Author: Carrillo‐Salinas, Francisco J. ; Mestre, Leyre ; Guaza, Carmen ; Yong, V. Wee ; Mecha, Miriam ; Feliu, Ana

AbstractThe failure to remyelinate and regenerate is a critical impediment to recovery in multiple sclerosis (MS), resulting in severe dysfunction and disability. The chondroitin sulfate proteoglycans (CSPGs) that accumulate in MS lesions are thought to be linked to the failure to regenerate, impeding oligodendrocyte precursor cell (OPC) differentiation and neuronal growth. The potential of endocannabinoids to influence MS progression may reflect their capacity to enhance repair processes. Here, we investigated how 2‐arachidonoylglycerol (2‐AG) may affect the production of the CSPGs neurocan and brevican by astrocytes in culture. In addition, we studied whether 2‐AG promotes oligodendrocyte differentiation under inhibitory conditions in vitro. Following treatment with 2‐AG or by enhancing its endogenous tone through the use of inhibitors of its hydrolytic enzymes, CSPG production by rat and human TGF‐β1 stimulated astrocytes was reduced. These effects of 2‐AG might reflect its influence on TGF‐β1/SMAD pathway, signaling that is involved in CSPG upregulation. The matrix generated from 2‐AG‐treated astrocytes is less inhibitory to oligodendrocyte differentiation and significantly, 2‐AG administration directly promotes the differentiation of rat and human oligodendrocytes cultured under inhibitory conditions. Overall, the data obtained favor targeting the endocannabinoid system to neutralize CSPG accumulation and to enhance oligodendrocyte differentiation.

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