Biology subjects

Kang, S.

Publications and source records attributed to Kang, S..

At least 109 records · Page 6Linked to original sources

bioRxiv2021

Dominant Effect Of Host Genetics On Skin Microbiota Composition In Homeostasis And Wound Healing

Animal microbiota have complex interactions with hosts and environment that determines its composition. Yet the ability of hosts to determine their microbiota composition is less well studied. In this study, to investigate the role host genetics in determining skin microbiota, we used 30 different mouse strains from the recombinant inbred panel, the Collaborative Cross. Murine skin microbiota composition was strongly dependent on murine strain with > 50% of the variation explained by murine strain. In particular, a quantitative trait locus on chromosome 4 associates both with Staphylococcus abundance and principal-component multi-trait analyses. Additionally, excisional wound associated changes in microbiota composition were not uniform across mouse strains and were host-specific, the genetic background accounting for about 40% of the variation in microbiota. Genetic background also had the highest effect on the healing speed of wounds accounting for over 50% of the variation while mouse age and microbiota composition change accounted only for 20% and 5% of the healing speed despite reaching statistical significance. In conclusion, host genetics has a significant impact on the skin microbiota composition during both homeostasis and wound healing. These findings have long reaching implications in our understanding of associations between microbiota dysbiosis and disease.

systems biology↗

bioRxiv2021

Rapid Electronic Diagnostics of Ebola Virus with Synthetic Nanobody-Conjugated Gold Nanoparticles

Successful control of emerging infectious diseases requires accelerated development of fast, affordable, and accessible assays to be widely implemented at a high frequency. Here we present a generalizable assay platform, nanobody-functionalized nanoparticles for rapid, electronic detection (Nano2RED), demonstrated in the detection of Ebola and COVID-19 antigens. To efficiently generate high-quality affinity reagents, synthetic nanobody co-binders and mono-binders with high affinity, specificity, and stability were selected by phage display screening of a vastly diverse, rationally randomized combinatorial library, bacterially expressed and site-specifically conjugated to gold nanoparticles (AuNPs) as multivalent in-solution sensors. Without requiring fluorescent labelling, washing, or enzymatic amplification, these AuNPs reliably transduce antigen binding signals upon mixing into physical AuNP aggregation and sedimentation processes, displaying antigen-dependent optical extinction readily detectable by spectrometry or simple electronic circuitry. With nanobodies against an Ebola virus secreted glycoprotein (sGP) and a SARS-CoV-2 spike protein receptor binding domain (RBD) as targets, Nano2RED showed a high sensitivity (limit of detection of [~]10 pg/mL for sGP and [~]40 pg/mL for RBD in diluted human serum), a high specificity, and a large dynamic range ([~]7 logs). Unlike conventional assays where slow mass transport for surface binding limits the assay time, Nano2RED features fast antigen diffusion at micrometer scale, and can be accelerated to deliver results within a few minutes. The rapid detection, low material cost (estimated < $0.01 per test), inexpensive and portable readout system (< $5 and < 100 cm3), and digital data output, make Nano2RED particularly suitable for screening of patient samples with simplified operation and accelerated data transmission. Our method is widely applicable for prototyping diagnostic assays for other antigens from new emerging viruses.

bioengineering↗

bioRxiv2021

The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis

CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/- Boris+/+, and Ctcf+/+Boris-/- males are fertile, Ctcf+/-Boris-/- (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are "toxic" to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.

genomics↗

bioRxiv2021

Transmission potential of Floridian Aedes aegypti mosquitoes for dengue virus serotype 4: Implications for estimating local dengue risk

Dengue virus serotype 4 (DENV-4) circulated in Aedes aegypti in 2016 and 2017 in Florida in the absence of human index cases, compelling a full assessment of local mosquito vector competence and DENV-4 risk. To better understand DENV-4 transmission risk in Florida, we used an expanded suite of tests to measure and compare the vector competence of both an established colony of Ae. aegypti (Orlando strain [ORL]) and a field-derived colony from Collier County, Florida in 2018 (COL) for a Haitian DENV-4 human field isolate and a DENV-4 laboratory strain (Philippines H241). We immediately noted that ORL saliva-positivity was higher for the field versus laboratory DENV-4 strains. In a subsequent comparison with the recent COL mosquito colony we also observed significantly higher midgut susceptibility of COL and ORL for the Haitian DENV-4 field strain, and significantly higher saliva-positivity rate for COL, although overall saliva virus titers were similar between the two. These data point to a potential midgut infection barrier for the DENV-4 laboratory strain for both mosquito colonies and that the marked difference in transmission potential estimates hinge on virus-vector combinations. Our study highlights the importance of leveraging an expanded suite of testing methods with emphasis on utilizing local mosquito populations and field relevant dengue serotypes and strains to accurately estimate transmission risk in a given setting. ImportanceDENV-4 was found circulating in Florida (FL) Ae. aegypti mosquitoes in the absence of human index cases in the state (2016-2017). How DENV-4 was maintained locally is unclear, presenting a major gap in our understanding of DENV-4 public health risk. We determined the baseline arbovirus transmission potential of laboratory and field colonies of Ae. aegypti for both laboratory and field isolates of DENV-4. We observed high transmission potential of field populations of Ae. aegypti and evidence of higher vertical transmission of the DENV-4 field isolate, providing clues to the possible mechanism of undetected DENV-4 maintenance in the state. Our findings also move the field forward in the development of best practices for evaluating arbovirus vector competence, with evidence that transmission potential estimates vary depending on the mosquito-virus combinations. These data emphasize the poor suitability of lab-established virus strains and the high relevance of field-derived mosquito populations in estimating transmission risk.

microbiology↗

bioRxiv2021

Non-canonical function of the Sex-lethal gene controls the protogyny phenotype in Drosophila melanogaster

Many animal species exhibit sex differences in the time period prior to reaching sexual maturity. However, the underlying mechanism for such biased maturation remains poorly understood. Females of the fruit fly Drosophila melanogaster eclose 4 h faster on average than males, owing to differences in the pupal period between the sexes; this characteristic is referred to as the protogyny phenotype. Here, we aimed to elucidate the mechanism underlying the protogyny phenotype in the fruit fly using our newly developed Drosophila Individual Activity Monitoring and Detecting System (DIAMonDS), which can continuously detect the precise timing of both pupariation and eclosion of individual flies. Via this system, following the laying of eggs, we detected the precise time points of pupariation and eclosion of a large number of individual flies simultaneously and succeeded in identifying the tiny differences in pupal duration between females and males. We first explored the role of physiological sex by establishing transgender flies via knockdown of the sex-determination gene, transformer (tra) and its co-factor tra2, which retained the protogyny phenotype. In addition, disruption of dosage compensation by male-specific lethal (msl-2) knockdown did not affect the protogyny phenotype. The Drosophila master sex switch gene--Sxl promotes female differentiation via tra and turns off male dosage compensation through the repression of msl-2. However, we observed that stage-specific whole-body knockdown and mutation of Sxl induced disturbance of the protogyny phenotype. These results suggest that an additional, non-canonical function of Sxl involves establishing the protogyny phenotype in D. melanogaster. Author summaryA wide variety of animals show differences in time points of sexual maturation between sexes. For example, in many mammals, including human beings, females mature faster than males. This maturation often takes several months or years, and precisely detecting the time point of maturation is challenging, because of the continuity of growth, especially in mammals. Moreover, the reason behind the difference in sexual maturation time points between sexes is not fully understood. The fruit fly Drosophila--a model organism--also shows biased maturation between the sexes, with females emerging 4 h faster than males (a characteristic known as the protogyny phenotype). To understand the mechanism underlying the protogyny phenotype, we used our newly developed system, Drosophila Individual Activity Monitoring and Detecting System (DIAMonDS), to detect the precise eclosion point in individual fruit flies. Surprisingly, our analysis of transgender flies obtained by knockdown and overexpression techniques indicated that a physiological gender might not be necessary requirement for protogyny and that a non-canonical novel function of the fruit fly master sex switch gene, Sxl, regulates protogyny in fruit flies.

genetics↗

bioRxiv2020

Clustered Rapid Induction of Apoptosis Limits ZIKV and DENV-2 Proliferation in the Midguts of Aedes aegypti

Inter-host transmission of pathogenic arboviruses such as dengue virus (DENV) and Zika virus (ZIKV) requires systemic infection of the mosquito vector. Successful systemic infection requires initial viral entry and proliferation in the midgut cells of the mosquito followed by dissemination to secondary tissues and eventual entry into salivary glands1. Lack of arbovirus proliferation in midgut cells has been observed in several Aedes aegypti strains2, but the midgut antiviral responses underlying this phenomenon are not yet fully understood. We report here that there is a rapid induction of apoptosis (RIA) in the Aedes aegypti midgut epithelium within 2 hours of infection with DENV-2 or ZIKV in both in vivo blood-feeding and ex vivo midgut infection models. Inhibition of RIA led to increased virus proliferation in the midgut, implicating RIA as an innate immune mechanism mediating midgut infection in this mosquito vector.

microbiology↗

bioRxiv2020

High-throughput phenotypic characterization of zebrafish CRISPR mutants of DNA repair genes

A systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental techniques. Here, we generated zebrafish loss-of-function mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. High-throughput phenotypic characterization of our mutant collection revealed that three genes (atad5a, ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1, atrip, ino80, mre11a, shfm1, telo2, wrn) are required for growth and development during juvenile stage and six genes (blm, brca2, fanci, rad51, rad54l, rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a, brca2, polk, rad51, shfm1, xrcc1) displayed hypersensitivity to DNA damage agents. Further characterization of atad5a-/- mutants demonstrate that Atad5a is required for normal brain development and hematopoiesis. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level.

developmental biology↗

bioRxiv2020

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.

molecular biology↗

bioRxiv2020

Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors

The number of new cases world-wide for the COVID-19 disease is increasing dramatically, while efforts to contain Severe Acute Respiratory Syndrome Coronavirus 2 is producing varied results in different countries. There are three key SARS-CoV-2 enzymes potentially targetable with antivirals: papain-like protease (PLpro), main protease (Mpro), and RNA-dependent RNA polymerase. Of these, PLpro is an especially attractive target because it plays an essential role in several viral replication processes, including cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex (RTC), and disruption of host viral response machinery to facilitate viral proliferation and replication. Moreover, this enzyme is conserved across different coronaviruses and promising inhibitors have already been discovered for its SARS-CoV variant. Here we report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the enzyme from SARS-CoV-2 in both wild-type and mutant forms. These efforts include the first structures of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors, determined at 1.60-2.70 Angstroms. This collection of structures provides fundamental molecular and mechanistic insight to PLpro, and critically, illustrates details for inhibitors recognition and interactions. All presented compounds inhibit the peptidase activity of PLpro in vitro, and some molecules block SARS-CoV-2 replication in cell culture assays. These collated findings will accelerate further structure-based drug design efforts targeting PLpro, with the ultimate goal of identifying high-affinity inhibitors of clinical value for SARS-CoV-2.

molecular biology↗

bioRxiv2020

Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2

ABSTRACTSARS-CoV-2 Nsp15 is a uridylate-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family. It degrades the polyuridine extensions in (-) sense strand of viral RNA and some non-translated RNA on (+) sense strand. This activity seems to be responsible for the interference with the innate immune response and evasion of host pattern recognition. Nsp15 is highly conserved in coronaviruses suggesting that its activity is important for virus replication. Here we report first structures with bound nucleotides and show that SARS-CoV-2 Nsp15 specifically recognizes U in a pattern previously predicted for EndoU. In the presence of manganese ions, the enzyme cleaves unpaired RNAs. Inhibitors of Nsp15 have been reported but not actively pursued into therapeutics. The current COVID-19 pandemic brought to attention the repurposing of existing drugs and the rapid identification of new antiviral compounds. Tipiracil is an FDA approved drug that is used with trifluridine in the treatment of colorectal cancer. Here, we combine crystallography, biochemical and whole cell assays, and show that this compound inhibits SARS-CoV-2 Nsp15 and interacts with the uridine binding pocket of the enzyme’s active site, providing basis for the uracil scaffold-based drug development.Competing Interest StatementThe authors have declared no competing interest.View Full Text

molecular biology↗

bioRxiv2020

The Drosophila Individual Activity Monitoring and Detection System (DIAMonDS)

Here, we have developed DIAMonDS (Drosophila Individual Activity Monitoring and Detection System) comprising time-lapse imaging by a charge-coupled device (CCD) flatbed scanner and Sapphire, a novel algorithm and web application. DIAMonDS automatically and sequentially identified the transition time points of multiple life cycle events such as pupariation, eclosion, and death in individual flies at high temporal resolution and on a large scale. DIAMonDS performed simultaneous multiple scans to measure individual deaths ([≤] 1,152 flies per scanner) and pupariation and eclosion timings ([≤] 288 flies per scanner) under various chemical exposures, environmental conditions, and genetic backgrounds. DIAMonDS correctly identified 74-85% of the pupariation and eclosion events and [~]92% of the death events within {+/-}10 scanning frames. This system is a powerful tool for studying the influences of genetic and environmental factors on fruit flies and efficient, high-throughput genetic and chemical screening in drug discovery.

developmental biology↗

bioRxiv2020

Skeletal muscle DNMT3A plays a necessary role in endurance exercise by regulating oxidative capacity of red muscles

Exercise interventions alter the DNA methylation profile in skeletal muscle, yet little is known about the role of the DNA methylation machinery in exercise capacity. In this study, we found that in oxidative red muscle, DNMT3A expression increases greatly following a bout of endurance exercise. Mice lacking Dnmt3a in skeletal muscle fibers had reduced tolerance to endurance exercise, accompanied by reduced oxidative capacity and reduced mitochondrial counts. Moreover, during exercise, the knockout muscles overproduced reactive oxygen species (ROS), which are major contributors to muscle dysfunction. In mechanistic terms, we demonstrated that Aldh1l1 is a key target of repression by DNMT3A in red muscles. DNMT3A directly regulated the Aldh1l1 transcription by binding to the Aldh1l1 promoter region and altering DNA methylation and histone modification. Enforcing ALDH1L1 expression, leading to elevated NADPH, led to overproduction of ROS by the NADPH oxidase complex (NOX) in myotubes, ultimately resulting in mitochondrial defects. Moreover, both genetic inhibition of ALDH1L1 and pharmacological inhibition of NOX rescued oxidative stress and mitochondrial decline in Dnmt3a-deficient myotubes, confirming the essential role of ALDH1L1-dependent ROS generation as a downstream effector of DNMT3A loss of function. Together, our results reveal that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.

cell biology↗

bioRxiv2020

De novo synthesis and salvage pathway coordinately regulates polyamine homeostasis and determines T cell proliferation and function.

Robust and effective T cell-mediated immune responses require proper allocation of metabolic resources through metabolic pathways to sustain the energetically costly immune response. As an essential class of polycationic metabolites ubiquitously present in all living organisms, the polyamine pool is tightly regulated by biosynthesis and salvage pathway. We demonstrated that arginine is a major carbon donor and glutamine is a minor carbon donor for polyamine biosynthesis in T cells. Accordingly, the dependence of T cells can be partially relieved by replenishing the polyamine pool. In response to the blockage of de novo synthesis, T cells can rapidly restore the polyamine pool through a compensatory increase in polyamine uptake from the environment, indicating a layer of metabolic plasticity. Simultaneously blocking synthesis and uptake depletes the intracellular PA pool, inhibits T cell proliferation, suppresses T cell inflammation, indicating the potential therapeutic value of targeting the polyamine for managing inflammatory and autoimmune diseases.

cell biology↗

bioRxiv2020

The integrin-mediated adhesome complex, essential to multicellularity, is present in the most recent common ancestor of animals, fungi, and amoebae

Integrins are transmembrane receptor proteins that activate signal transduction pathways upon extracellular matrix binding. The Integrin Mediated Adhesion Complex (IMAC), mediates various cell physiological process. The IMAC was thought to be an animal specific machinery until over the last decade these complexes were discovered in Obazoa, the group containing animals, fungi, and several microbial eukaryote lineages. Amoebozoa is the eukaryotic supergroup sister to Obazoa. Even though Amoebozoa represents the closest outgroup to Obazoa, little genomic-level data and attention to gene inventories has been given to the supergroup. To examine the evolutionary history of the IMAC, we examine gene inventories of deeply sampled set of 100+ Amoebozoa taxa, including new data from several taxa. From these robust data sampled from the entire breadth of known amoebozoan clades, we show the presence of an ancestral complex of integrin adhesion proteins that predate the evolution of the Amoebozoa. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought. Co-option of an ancient protein complex was key to the emergence of animal type multicellularity. The role of the IMAC in a unicellular context is unknown but must also play a critical role for at least some unicellular organisms.

evolutionary biology↗

bioRxiv2020

Pathogenic LRRK2 R1441C mutation is associated with striatal alterations

LRRK2 mutations are associated with both familial and sporadic forms of Parkinsons disease (PD). Convergent evidence suggests that LRRK2 plays critical roles in regulating striatal function. Here, by using knock-in mouse lines that express the two most common LRRK2 pathogenic mutations--G2019S and R1441C--we investigated how pathogenic LRRK2 mutations altered striatal physiology. We found that R1441C mice displayed a reduced nigrostriatal dopamine release and hypoexcitability in indirect-pathway striatal projection neurons. These alterations were associated with an impaired striatal-dependent motor learning. This deficit in motor learning was rescued following the subchronic administration of the LRRK2 kinase inhibitor Mli-2. In contrast, though a decreased release of dopamine was observed in the G2019S knock-in mice no concomitant cellular and behavioral alterations were found. In summary, our data argue that the impact of LRRK2 mutations cannot be simply generalized. Our findings offer mechanistic insights for devising treatment strategies for PD patients.

neuroscience↗

bioRxiv2020

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 [A] crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the {beta}-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

molecular biology↗

bioRxiv2020

Under-the-radar dengue virus infections in natural populations of Aedes aegypti mosquitoes

The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort on the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the metavirome of four populations of Ae. aegypti mosquitoes collected in 2016-2017 from Manatee County, Florida. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a two-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, as well as explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of these DENV4 infections in Ae. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. ImportanceSince 1999, dengue outbreaks in the continental United States (U.S.) involving local transmission have occurred episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from endemic countries. To date, the U.S. public health response to dengue outbreaks is largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of non-outbreak DENV4 transmission and maintenance within a local mosquito vector population in the continental U.S.in the absence of a human case during a two-year time period. Our data suggest that molecular surveillance of mosquito populations in high-risk, high tourism areas of the U.S., may allow for proactive, targeted vector control before potential arbovirus outbreaks.

ecology↗

bioRxiv2020

Pathway-specific deregulation of striatal excitatory synapses in LRRK2 mutations

LRRK2 is a kinase expressed in striatal spiny projection neurons (SPNs), cells which lose dopaminergic input in Parkinsons disease (PD). R1441C and G2019S are the most common pathogenic mutations of LRRK2. How these mutations alter the structure and function of individual synapses on direct and indirect pathway SPNs is unknown and may reveal pre-clinical changes in dopamine-recipient neurons that predispose towards disease. Here, R1441C and G2019S knock-in mice enabled thorough evaluation of dendritic spines and synapses on pathway-identified SPNs. Biochemical synaptic preparations and super-resolution imaging revealed increased levels and altered organization of glutamatergic AMPA receptors in LRRK2 mutants. Relatedly, decreased frequency of excitatory post-synaptic currents accompanied changes in dendritic spine nano-architecture, and single-synapse currents, evaluated using 2-photon glutamate uncaging. Overall, LRRK2 mutations reshaped synaptic structure and function, an effect exaggerated in R1441C dSPNs. These data open the possibility of new neuroprotective therapies aimed at SPN synapse function, prior to disease onset.

neuroscience↗