Biology subjects

Seong, J. Y.

Publications and source records attributed to Seong, J. Y..

5 recordsLinked to original sources

bioRxiv2024

FAM19A5 Deficiency Mitigates the Aβ Plaque Burden and Improves Cognition in Mouse Models of Alzheimer's Disease

FAM19A5, a novel secretory protein highly expressed in the brain, is potentially associated with the progression of Alzheimers disease (AD). However, its role in the AD brain remains unclear. Here, we investigated the potential function of FAM19A5 in the context of AD. We generated APP/PS1 mice with partial FAM19A5 deficiency, termed APP/PS1/FAM19A5+/LacZ mice. Compared to control APP/PS1 mice, APP/PS1/FAM19A5+/LacZ mice exhibited significantly lower A{beta} plaque density, suggesting that FAM19A5 reduction mitigates A{beta} plaque formation. Notably, partial FAM19A5 depletion also prolonged the lifespan of the APP/PS1 mice. To further explore the therapeutic potential of targeting FAM19A5, we developed an anti-FAM19A5 antibody. Administration of this antibody to APP/PS1 mice significantly improved their performance in the novel object recognition test, demonstrating enhanced cognitive function. This effect was reproduced in 5XFAD mice, a model of early-onset AD characterized by rapid A{beta} accumulation. Additionally, anti-FAM19A5 antibody treatment in 5XFAD mice led to increased spontaneous alternation behavior in the Y-maze test, indicating improved spatial working memory. These findings suggest that anti-FAM19A5 antibodies may be a promising therapeutic strategy for AD by reducing A{beta} plaques and improving cognitive function.

neuroscience↗

bioRxiv2024

Partial FAM19A5 Deficiency in Mice Leads to Disrupted Spine Maturation, Hyperactivity and Altered Fear Response

The FAM19A5 polypeptide, encoded by the TAFA5 gene, is evolutionarily conserved among vertebral species. This protein is predominantly expressed in the brain, highlighting its crucial role in the central nervous system. Here, we investigated the potential roles of FAM19A5 in brain development and behavior using a FAM19A5-LacZ KI mouse model. This model exhibited a partial reduction in the FAM19A5 protein level. FAM19A5-LacZ KI mice displayed no significant alterations in gross brain structure but alterations in dendritic spine distribution, with a bias toward immature forms. These mice also had lower body weights. Behavioral tests revealed that compared with their wild-type littermates, FAM19A5-LacZ KI mice displayed hyperactivity and a delayed innate fear response. These findings suggest that FAM19A5 plays a role in regulating spine formation and maintenance, thereby contributing to neural connectivity and behavior.

neuroscience↗

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↗

bioRxiv2020

Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knock-out, and LacZ knock-in mice.

FAM19A5 is a novel secretory protein primarily expressed in the brain. However, a recent study reported that FAM19A5 is an adipocyte-derived adipokine that regulates vascular smooth muscle function through sphingosine-1-phosphate receptor 2 (S1PR2). In our study, we investigated FAM19A5 transcript and protein levels in peripheral tissues, including adipose tissues, from wild-type, FAM19A5 knockout, and FAM19A5 LacZ knockin mice. We found that FAM19A5 transcript levels in the central nervous system were much greater than those in any of the peripheral tissues, including adipose tissues. Furthermore, the FAM19A5 protein levels in adipose and reproductive tissues were below detectable limits for Western blot analysis. Additionally, we found that the FAM19A5 protein did not interact with S1PR2 in terms of G protein-mediated signal transduction, {beta}-arrestin recruitment, or ligand-mediated internalization. Taken together, our findings revealed basal levels of FAM19A5 transcripts and proteins in peripheral tissues, confirming its primary expression in the central nervous system and lack of significant interaction with S1PR2.

genetics↗