Biology subjects

Hwang, S. W.

Publications and source records attributed to Hwang, S. W..

3 recordsLinked to original sources

bioRxiv2024

Decorin promotes cardiac organoid maturation by activating AMPK-PGC1A pathway to enhance cardiac metabolism and mitophagy

RationaleCardiac organoids (COs) are advanced models for investigating heart development and disease, while require maturation to resemble the structural and functional characteristics of the human heart. ObjectiveThis study reveals the role of Decorin (DCN) contributes to the mature and vascularized COs and assesses the biological mechanism responsible for CO maturation. Methods and ResultsDCN-treated COs exhibit structural maturation involving aligned sarcomere, mitochondria, and t-tubule structures, and vessel formations, as well as functional maturation involving synchronized contraction-relaxation, Ca2+ transient, and increases ion channel expressions. DCN-treated COs also show metabolic maturation, including enhanced fatty acid oxidation and increased mitophagy. Transcriptional profiling results indicate that DCN-treated COs have increased levels of AMPK signaling and mitophagy. In DCN-treated COs, AMPK knockdown affects mitochondrial biogenesis, cardiac metabolism, ion channels, and mitophagy. ConclusionsThese findings indicate that DCN is crucial for development of mature, vascularized COs and that CO maturation is primarily regulated through AMPK signaling, which is triggered by DCN. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/599970v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1333cfaorg.highwire.dtl.DTLVardef@e842baorg.highwire.dtl.DTLVardef@74ce1corg.highwire.dtl.DTLVardef@87ad38_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHIC ABSTRACTC_FLOATNO A graphic abstract is available for this article. DCN enhances metabolic maturation in COs by AMPK-triggered regulation of the glycolysis, fatty acid oxidation, and mitophagy. C_FIG

developmental biology↗

bioRxiv2023

Antibody-based immunotherapy targeting FAM19A5 reverses synaptic loss and improves cognitive function in Alzheimer's disease.

IntroductionAlzheimers disease (AD) is characterized by the dysregulation of synaptic balance, with progressive loss of synapses outpacing formation, ultimately leading to cognitive decline. However, the lack of effective strategies for restoring lost synapses poses a major barrier to improving clinical outcomes. MethodsWe developed NS101, a monoclonal antibody targeting FAM19A5, a brain-secreted protein. Its preclinical efficacy in restoring synapses and cognition was evaluated using APP/PS1 and P301S mice. The clinical safety and target engagement of NS101 were examined in human participants. ResultsFAM19A5 binds to LRRC4B, a postsynaptic adhesion molecule, leading to synapse reduction. Blocking this interaction with NS101 normalized the rate of synapse elimination in AD mice. This synaptic rebalancing restored the number and function of synapses, resulting in improved cognition. Systemically administered NS101 facilitated the transport of brain FAM19A5 into the bloodstream. DiscussionTargeting FAM19A5 may hold clinical promise for treating AD by restoring synaptic balance.

neuroscience↗

bioRxiv2020

FAM19A5l affects mustard oil-induced peripheral nociception in zebrafish

Family with sequence similarity 19 (chemokine (C-C motif)-like), member A5 (FAM19A5) is a chemokine-like secretory protein recently identified to be involved in the regulation of osteoclast formation, post-injury neointima formation, and depression. Here, we identified FAM19A5l, an orthologous zebrafish gene that originated from a common ancestral FAM19A5 gene. FAM19A5l was expressed in trigeminal and dorsal root ganglion neurons as well as distinct neuronal subsets of the central nervous system of zebrafish. Interestingly, FAM19A5l+ trigeminal neurons were nociceptors that co-localized with TRPA1b and TRPV1, and responded to mustard-oil treatment. Behavioral analysis revealed that the nociceptive response to mustard oil decreased in FAM19A5l-knockout zebrafish larvae. In addition, TRPA1b and NGFa mRNA levels were down- and up-regulated in FAM19A5l-knockout and - overexpressing transgenic zebrafish, respectively. Together, our data suggested that FAM19A5l played a role in nociceptive responses to mustard oil by regulating TRPA1b and NGFa expression in zebrafish.

neuroscience↗