Biology subjects

Kang, S. S.

Publications and source records attributed to Kang, S. S..

6 recordsLinked to original sources

bioRxiv2026

Splanchnic-spinal transmission of gut-initiated α-synucleinopathy

Gut-initiated -synucleinopathy is proposed to spread from the gastrointestinal tract to the CNS, contributing to Parkinson's disease (PD), but whether routes beyond the vagus nerve are involved remains unclear. Using complementary intracolonic rotenone and gastroduodenal -synuclein PFF models, we combined pathway-specific surgical interruption with longitudinal behavioral analysis and anatomical mapping of pathological -synuclein. In the intracolonic rotenone model, interruption of the prevertebral ganglia/splanchnic-spinal axis more strongly attenuated behavioral deficits and -synuclein pathology than vagotomy. In the gastroduodenal PFF model, both vagal and splanchnic-spinal pathways contributed to pathology propagation. Early after PFF inoculation, pathological -synuclein was detected in peripheral neural structures associated with both routes. Consistent with these findings, spinal pathology was evident in human PD. Together, these results identify the splanchnic-spinal pathway as a key component of body-first Parkinson's disease, broadening current models of peripheral-to-central disease progression and informing efforts to target early peripheral disease progression.

neuroscience↗

bioRxiv2023

Interaction between PSD 95 and TRPV4 through PDZ domain controls TRPV4's localization and activity.

The TRPV4 cation channel, is expressed in a broad range of tissues where it participates in generation of Ca2+ signal and/or depolarization of membrane potential. Here, we identified post synaptic density protein 95 (PSD95) as an interacting protein of this epithelial Ca2+ channel using confocal microscopy analysis and immunological assay. Using co-immunoprecipitation assays, we demonstrated that PSD95 was part of the TRPV4 protein complex. PSD95 protein was specifically associated with the C-terminal tail of TRPV4 to form a complex. A TRPV4 tail deletion mutant ({Delta}DAPL871: 4d) exhibited a diminished capacity to bind PSD95. Confocal microscopy analysis suggested that apical localization of TRPV4 required PSD95-TRPV4 interaction. Our data clearly suggest that formation of a complex between TRPV4 and PSD95 can regulate TRPV4 membrane localization. Both TRPV4 Ca2+ channel and its autophagy activity of 4d were reduced by more than 80% compared to those of the TRPV4 wild type. Our observation suggests that PSD95-TRPV4 complex plays crucial roles in routing TRPV4 to the apical plasma membrane and maintaining its authentic Ca2+ channel and biological function. CapsuleO_ST_ABSBackgroundC_ST_ABSTRPV4 contain putative PDZ tail motif (DAPL871). ResultsDeletion of TRPV4 tail PDZ motif fails to interact with PSD95 PDZ III domain. ConclusionTRPV4 tail is an authentic PDZ motif to interact with PSD95. SignificanceInteraction between TRPV4 and PSD95 requires for its proper biological functions.

cell biology↗

bioRxiv2022

Brain Atlas for Glycoprotein Hormone Receptors at Single-Transcript Level

There is increasing evidence that anterior pituitary hormones, traditionally thought to have unitary functions in regulating single endocrine targets, act on multiple somatic tissues, such as bone, fat, and liver. There is also emerging evidence for anterior pituitary hormone action on brain receptors in mediating central neural and peripheral somatic functions. Here, we have created the most comprehensive neuroanatomical atlas on the expression of TSHRs, LHCGRs and FSHRs. We have used RNAscope, a technology that allows the detection of mRNA at single-transcript level, together with protein level validation, to document Tshr expression in 173 and Fshr expression in 353 brain regions, nuclei and sub-nuclei identified using the Atlas for the Mouse Brain in Stereotaxic Coordinates. We also identified Lhcgr transcripts in 401 brain regions, nuclei and sub-nuclei. Complementarily, we used ViewRNA, another single-transcript detection technology, to establish the expression of FSHRs in human brain samples, where transcripts were co-localized in MALAT1-positive neurons. In addition, we show high expression for all three receptors in the ventricular region--with yet unknown functions. Intriguingly, Tshr and Fshr expression in the ependymal layer of the third ventricle was similar to that of the thyroid follicular cells and testicular Sertoli cells, respectively. TSHRs were expressed specifically in tanycytes. In contrast, Fshrs were localized to NeuN-positive neurons in the granular layer of the dentate gyrus in murine and human brain--both are Alzheimers disease vulnerable regions. Our atlas thus provides a vital resource for scientists to explore the link between the stimulation or inactivation of brain glycoprotein hormone receptors on somatic function. New actionable pathways for human disease may be unmasked through further studies.

neuroscience↗

bioRxiv2020

SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients

Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural proteins corroborated adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and numerous iPSC-cardiomyocytes lacking nuclear DNA. Human autopsy specimens from COVID-19 patients displayed similar sarcomeric disruption, as well as cardiomyocytes without DNA staining. These striking cytopathic features provide new insights into SARS-CoV-2 induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise serious concerns about the long-term consequences of COVID-19.

cell biology↗

bioRxiv2019

The Norepinephrine Metabolite DOPEGAL Confers Locus Coeruleus Tau Vulnerability and Propagation via Asparagine Endopeptidase

Aberrant Tau inclusions in the locus coeruleus (LC) are the earliest detectable Alzheimers disease (AD)-like neuropathology in the human brain; however, why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in disease and whether the LC might seed the stereotypical spread of Tau pathology to the rest of the brain remain unclear. Here we show that 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL), which is produced exclusively in noradrenergic neurons by monoamine oxidase A (MAO-A) metabolism of norepinephrine (NE), activates asparagine endopeptidase (AEP) that cleaves Tau at residue N368 into aggregation- and propagation-prone forms, thereby leading to LC degeneration and the spread of Tau pathology. DOPEGAL triggers AEP-cleaved Tau aggregation in vitro and in intact cells, resulting in LC neurotoxicity and propagation of pathology to the forebrain. Thus, our findings reveal a novel molecular mechanism underlying the selective vulnerability of LC neurons in AD.

neuroscience↗

bioRxiv2017

Translational Profiling Of Microglia Reveals Artifacts Of Cell Sorting

Microglia are the resident innate immune population of the central nervous system that constantly survey and influence their local environment. Transcriptomic profiling has led to significant advances in our understanding of microglia in several disease states, but tissue dissociation and purification of microglia is known to lead to cellular activation. Here we use RiboTag translational RNAseq profiling to demonstrate that commonly used cell sorting methods lead to a fundamental alteration of the microglial transcriptome, with several transcripts that can be used to mark artifacts of isolation. Microglial RiboTag RNAseq profiling after peripheral immune challenge with lipopolysaccharide demonstrates unique transcriptional targets that are not evident using cell sorting methodology. Finally, we applied our technique to reveal novel shared and distinct pathways when comparing microglial transcriptomes after peripheral challenge with bacterial or viral mimetics. This study has broad implications for approaches that examine microglial transcriptomes in normal and pathological states.\n\nSummaryKang et al. demonstrate artifactual induction of microglial transcripts associated with cell sorting. Using RiboTag translational profiling methodology, several markers of cell sorting artifact were revealed. Furthermore, RiboTag isolation unveiled changes in microglial transcriptomes following systemic inflammation that would otherwise have been masked by artifacts of cell sorting.

neuroscience↗