Last update 01 Nov 2024

BCAN x Chondroitin sulfate proteoglycans

Last update 01 Nov 2024

Basic Info

Related Targets

BCANChondroitin sulfate proteoglycans

Drugs associated with BCAN x Chondroitin sulfate proteoglycans

HG-1280

Target

BCAN x Chondroitin sulfate proteoglycans

Mechanism

BCAN modulators [+1]

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BCAN x Chondroitin sulfate proteoglycans

100 Translational Medicine associated with BCAN x Chondroitin sulfate proteoglycans

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

Literatures (Medical) associated with BCAN x Chondroitin sulfate proteoglycans

08 Jul 2024·ACS Biomaterials Science & Engineering

Mechanobiological Modulation of In Vitro Astrocyte Reactivity Using Variable Gel Stiffness

Article

Author: Porcionatto, Marimelia A ; Madias, Marianne I ; Kwon, Ester J ; Engler, Adam J ; Delgado-Garcia, Lina M ; Kandell, Rebecca M ; C Benincasa, Julia

After traumatic brain injury, the brain extracellular matrix undergoes structural rearrangement due to changes in matrix composition, activation of proteases, and deposition of chondroitin sulfate proteoglycans by reactive astrocytes to produce the glial scar. These changes lead to a softening of the tissue, where the stiffness of the contusion "core" and peripheral "pericontusional" regions becomes softer than that of healthy tissue. Pioneering mechanotransduction studies have shown that soft substrates upregulate intermediate filament proteins in reactive astrocytes; however, many other aspects of astrocyte biology remain unclear. Here, we developed a platform for the culture of cortical astrocytes using polyacrylamide (PA) gels of varying stiffness (measured in Pascal; Pa) to mimic injury-related regions in order to investigate the effects of tissue stiffness on astrocyte reactivity and morphology. Our results show that substrate stiffness influences astrocyte phenotype; soft 300 Pa substrates led to increased GFAP immunoreactivity, proliferation, and complexity of processes. Intermediate 800 Pa substrates increased Aggrecan⁺, Brevican⁺, and Neurocan⁺ astrocytes. The stiffest 1 kPa substrates led to astrocytes with basal morphologies, similar to a physiological state. These results advance our understanding of astrocyte mechanotransduction processes and provide evidence of how substrates with engineered stiffness can mimic the injury microenvironment.

01 Jul 2024·Molecular Psychiatry

Molecular profiling of the hippocampus of children with autism spectrum disorder

Article

Author: Vandewege, Michael W ; Challagundla, Lavanya ; Pantazopoulos, Harry ; Showmaker, Kurt C ; Rexrode, Lindsay E ; Hilton, Keauna ; Theoharides, Theoharis C ; Martin, Brigitte E ; Garrett, Michael R ; Gardiner, Alex ; Gisabella, Barbara ; Antonyraj, Rhenius B ; Valeri, Jake ; Blair, Estelle ; Hartley, Joshua ; Bollavarapu, Ratna

AbstractSeveral lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling. There is a lack of information regarding the molecular pathology of the hippocampus in ASD. We conducted RNAseq profiling on postmortem human brain samples containing the hippocampus from male children with ASD (n = 7) and normal male children (3–14 yrs old), (n = 6) from the NIH NeuroBioBank. Gene expression profiling analysis implicated molecular pathways involved in extracellular matrix organization, neurodevelopment, synaptic regulation, and immune system signaling. qRT-PCR and Western blotting were used to confirm several of the top markers identified. The CSPG protein BCAN was examined with multiplex immunofluorescence to analyze cell-type specific expression of BCAN and astrocyte morphology. We observed decreased expression of synaptic proteins PSD95 (p < 0.02) and SYN1 (p < 0.02), increased expression of the extracellular matrix (ECM) protease MMP9 (p < 0.03), and decreased expression of MEF2C (p < 0.03). We also observed increased BCAN expression with astrocytes in children with ASD, together with altered astrocyte morphology. Our results point to alterations in immune system signaling, glia cell differentiation, and synaptic signaling in the hippocampus of children with ASD, together with alterations in extracellular matrix molecules. Furthermore, our results demonstrate altered expression of genes implicated in genetic studies of ASD including SYN1 and MEF2C.

01 Feb 2024·Advanced Therapeutics

In Vitro Assessment of Protamine Toxicity with Neural Cells, Its Therapeutic Potential to Counter Chondroitin Sulfate Mediated Neuron Inhibition, and Its Effects on Reactive Astrocytes

Article

Author: Funnell, Jessica L. ; Mendoza, Christina S. ; Bentley, Marvin ; Quinones, Geraldine B. ; Nelson, Derek W. ; Gilbert, Ryan J. ; Cheung, Conrad H.

AbstractMultiple therapies have been studied to ameliorate the neuroinhibitory cues present after traumatic injury to the central nervous system. Two previous in vitro studies have demonstrated the efficacy of the Food and Drug Administration‐approved cardiovascular therapeutic, protamine (PRM), to overcome neuroinhibitory cues presented by chondroitin sulfates; however, the effect of a wide range of PRM concentrations on neuronal and glial cells has not been evaluated. In this study, we investigate the therapeutic efficacy of PRM with primary cortical neurons, hippocampal neurons, mixed glial cultures, and astrocytes. The threshold for PRM toxicity is shown to be at or above 10 µg mL−1 depending on the cell population, that 10 µg mL−1 PRM enables neurons to overcome the inhibitory cues presented by chondroitin sulfate type A, and that soluble PRM allows neurons to more effectively overcome inhibition compared to a PRM coating. Changes in gene expression of reactive astrocytes is also assessed with soluble PRM and it is determined that PRM does not increase their neurotoxic phenotype and that PRM may reduce brevican and serpin transcription in cortical and spinal cord astrocytes. This is the first study to thoroughly assess the toxicity threshold of PRM with neural cells and study astrocyte response after acute exposure to PRM in vitro.

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