Biology subjects

Luo, Z.

Publications and source records attributed to Luo, Z..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

A spatial and cellular distribution of neurotropic virus infection in the mouse brain revealed by fMOST and single cell RNA-seq

Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both human and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques. In this study, we explore the use of fluorescence micro-optical sectioning tomography (fMOST) and single cell RNA sequencing (scRNA-seq) to map the spatial and cellular distribution of a representative neurotropic virus, rabies virus (RABV), in the whole brain. Mice were inoculated with a lethal dose of recombinant RABV expressing enhanced green fluorescent protein (EGFP) under different infection routes, and a three-dimensional view of the distribution of RABV in the whole mouse brain was obtained using fMOST. Meanwhile, we pinpointed the cellular distribution of RABV by utilizing scRNA-seq. Our fMOST data provide the first evidence that RABV can infect multiple nuclei related to fear independent of different infection routes. More surprisingly, scRNA-seq data indicate that besides neurons RABV can infect macrophages and NK cells in vivo. Collectively, this study draws a comprehensively spatial and cellular map of RABV infection in the mouse brain, providing a novel and insightful strategy to investigate the pathogenesis of neurotropic viruses.

microbiology↗

bioRxiv2021

scGAE: topology-preserving dimensionality reduction for single-cell RNA-seq data using graph autoencoder

Dimensionality reduction is crucial for the visualization and interpretation of the high-dimensional single-cell RNA sequencing (scRNA-seq) data. However, preserving topological structure among cells to low dimensional space remains a challenge. Here, we present the single-cell graph autoencoder (scGAE), a dimensionality reduction method that preserves topological structure in scRNA-seq data. scGAE builds a cell graph and uses a multitask-oriented graph autoencoder to preserve topological structure information and feature information in scRNA-seq data simultaneously. We further extended scGAE for scRNA-seq data visualization, clustering, and trajectory inference. Analyses of simulated data showed that scGAE accurately reconstructs developmental trajectory and separates discrete cell clusters under different scenarios, outperforming recently developed deep learning methods. Furthermore, implementation of scGAE on empirical data showed scGAE provided novel insights into cell developmental lineages and preserved inter-cluster distances.

bioinformatics↗

bioRxiv2021

Crystal structure determination of the armadillo repeat domain of Drosophila SARM1 using MIRAS phasing

We describe the crystal structure determination of the ARM domain of Drosophila SARM1 (dSARM1ARM), which required combination of a number of sources of phase information in order to obtain interpretable electron density maps. SARM1 is a central executioner of the process of axon degeneration, a common feature of the early phase of a range of neurodegenerative diseases. SARM1 is held in the inactive state in healthy axons by its N-terminal auto-inhibitory ARM domain, and is activated to cleave NAD+ upon injury, triggering the subsequent axon degeneration. To characterize the molecular mechanism of SARM1 activation, we sought to determine the crystal structure of the SARM1 ARM domain. Here we describe the recombinant production and crystallization of dSARM1ARM, as well as unconventional process used for structure determination. Crystals were obtained in the presence of NMN, a precursor of NAD+ and a potential activator of SARM1, only after in situ proteolysis of the N-terminal 63 residues. After molecular replacement attempts failed, we determined the crystal structure of dSARM1ARM at 1.65 [A] resolution using the MIRAS phasing technique with the program autoSHARP, combining data from the native, SeMet-labelled, and Br-soaked crystals. The structure will further our understanding of the regulation of SARM1.

biophysics↗

bioRxiv2021

Dual expression of Atoh1 and Ikzf2 promotes transformation of adult cochlear supporting cells into outer hair cells

Mammalian cochlear outer hair cells (OHCs) are essential for hearing. OHC degeneration causes severe hearing impairment. Previous attempts of regenerating new OHCs from cochlear supporting cells (SCs) had yielded cells lacking Prestin, a key motor protein for OHC function. Thus, regeneration of Prestin+ OHCs remains a challenge for repairing OHC damage in vivo. Here, we reported that successful in vivo conversion of adult cochlear SCs into Prestin+ OHC-like cells could be achieved by simultaneous expression of Atoh1 and Ikzf2, two key transcriptional factors necessary for OHC development. New OHC-like cells exhibited upregulation of hundreds of OHC genes and downregulation of SC genes. Single cell transcriptomic analysis demonstrated that the differentiation status of these OHC-like cells was much more advanced than previously achieved. Thus, we have established an efficient approach to promote regeneration of Prestin+ OHCs and paved the way for repairing damaged cochlea in vivo via transdifferentiation of SCs.

developmental biology↗

bioRxiv2020

Expanding diversity of Asgard archaea and the elusive ancestry of eukaryotes

Comparative analysis of 162 (nearly) complete genomes of Asgard archaea, including 75 not reported previously, substantially expands the phylogenetic and metabolic diversity of the Asgard superphylum, with six additional phyla proposed. Phylogenetic analysis does not strongly support origin of eukaryotes from within Asgard, leaning instead towards a three-domain topology, with eukaryotes branching outside archaea. Comprehensive protein domain analysis in the 162 Asgard genomes results in a major expansion of the set of eukaryote signature proteins (ESPs). The Asgard ESPs show variable phyletic distributions and domain architectures, suggestive of dynamic evolution via horizontal gene transfer (HGT), gene loss, gene duplication and domain shuffling. The results appear best compatible with the origin of the conserved core of eukaryote genes from an unknown ancestral lineage deep within or outside the extant archaeal diversity. Such hypothetical ancestors would accumulate components of the mobile archaeal eukaryome via extensive HGT, eventually, giving rise to eukaryote-like cells.

genomics↗

bioRxiv2020

Alisertib exerts KRAS allele specific anticancer effects in colorectal cancer

Colorectal cancer (CRC) is a common cancer causing substantial mortality and morbidity worldwide. Oncogene RAS mutations occur notably in [~]45% of CRCs, associated with a poor prognosis. KRAS is subject to multiple tiers of regulation, including kinase. Aurora kinases has been implicated in many types of tumor onsets and progression, making them as a promising therapeutic targets. Alisertib (ALS), selectively inhibits Aurora kinase A (AURKA) and exerts potent anticancer activities in vitro and in vivo studies, but the latent anticancer effect of ALS on CRC remains unclear in the context of different KRAS mutations. This study aimed to assess the effects of ALS on RAS signaling pathway in a panel of CRC lines expressing different KRAS alleles, including Caco-2 (KRAS WT), Colo-678 (KRAS G12D), SK-CO-1 (KRAS G12V), HCT116 (KRAS G13D), CCCL-18 (KRAS A146T), and HT29 (BRAF V600E). The results showed that ALS modulated the active form of KRAS in a RAS allele specific manner across the panel of CRC lines; ALS differentially regulated RAS signal via PI3K/Akt and MAPK pathways; and ALS induced apoptosis and autophagy in a RAS allele specific manner. Of note, in combination of ALS and MEK inhibitor, selumetinib, enhanced ALS regulatory effects in CRC lines in a RAS allele specific manner on apoptosis, autophagy, and cell growth. Taken together, this study suggests that ALS differentially regulates RAS signaling pathway and manipulates cell apoptosis and autophagy in RAS allele specific manner. The combinatorial approach of ALS and MEK inhibitor may represent a new therapeutic strategy for precision therapy of CRC in a RAS allele manner.

cancer biology↗

bioRxiv2020

Three-dimensional Printing of Customized Bioresorbable Airway Stents

Central airway obstruction is a life-threatening disorder causing a high physical and psychological burden to patients due to severe breathlessness and impaired quality of life. Standard-of-care airway stents are silicone tubes, which cause immediate relief, but are prone to migration, especially in growing patients, and require additional surgeries to be removed, which may cause further tissue damage. Customized airway stents with tailorable bioresorbability that can be produced in a reasonable time frame would be highly needed in the management of this disorder. Here, we report poly(D,L-lactide-co-{varepsilon}-caprolactone) methacrylate blends-based biomedical inks and their use for the rapid fabrication of customized and bioresorbable airway stents. The 3D printed materials are cytocompatible and exhibit silicone-like mechanical properties with suitable biodegradability. In vivo studies in healthy rabbits confirmed biocompatibility and showed that the stents stayed in place for 7 weeks after which they became radiographically invisible. The developed biomedical inks open promising perspectives for the rapid manufacturing of the customized medical devices for which high precision, tuneable elasticity and predictable degradation are sought-after.

bioengineering↗

bioRxiv2020

VirPreNet: A weighted ensemble convolutional neural network for the virulence prediction of influenza A virus using all 8 segments

MotivationInfluenza viruses are persistently threatening public health, causing annual epidemics and sporadic pandemics. The evolution of influenza viruses remains to be the main obstacle in the effectiveness of antiviral treatments due to rapid mutations. Previous work has been investigated to reveal the determinants of virulence of the influenza A virus. To further facilitate flu surveillance, explicit detection of influenza virulence is crucial to protect public health from potential future pandemics. ResultsIn this paper, we propose a weighted ensemble convolutional neural network for the virulence prediction of influenza A viruses named VirPreNet that uses all 8 segments. Firstly, mouse lethal dose 50 is exerted to label the virulence of infections into two classes, namely avirulent and virulent. A numerical representation of amino acids named ProtVec is applied to the 8-segments in a distributed manner to encode the biological sequences. After splittings and embeddings of influenza strains, the ensemble convolutional neural network is constructed as the base model on the influenza dataset of each segment, which serves as the VirPreNets main part. Followed by a linear layer, the initial predictive outcomes are integrated and assigned with different weights for the final prediction. The experimental results on the collected influenza dataset indicate that VirPreNet achieves state-of-the-art performance combining ProtVec with our proposed architecture. It outperforms baseline methods on the independent testing data. Moreover, our proposed model reveals the importance of PB2 and HA segments on the virulence prediction. We believe that our model may provide new insights into the investigation of influenza virulence. Contactyinr0002@e.ntu.edu.sg Availability and ImplementationCodes and data to generate the VirPreNet are publicly available at https://github.com/Rayin-saber/VirPreNet

bioinformatics↗

bioRxiv2020

Transposable Element-Gene Splicing Modulates the Transcriptional Landscape of Human Pluripotent Stem Cells

Transposable elements (TEs) occupy nearly 50% of mammalian genomes and are both potential dangers to genome stability and functional genetic elements. TEs can be expressed and exonised as part of a transcript, however, their full contribution to the transcript splicing remains unresolved. Here, guided by long and short read sequencing of RNAs, we show that 26% of coding and 65% of non-coding transcripts of human pluripotent stem cells (hPSCs) contain TEs. Different TE families have unique integration patterns with diverse consequences on RNA expression and function. We identify hPSC-specific splicing of endogenous retroviruses (ERVs) as well as LINE L1 elements into protein coding genes that generate TE-derived peptides. Finally, single cell RNA-seq reveals that proliferating hPSCs are dominated by ERV-containing transcripts, and subpopulations express SINE or LINE-containing transcripts. Overall, we demonstrate that TE splicing modulates the pluripotency transcriptome by enhancing and impairing transcript expression and generating novel transcripts and peptides.

genomics↗

bioRxiv2020

Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide

A newly emerging novel coronavirus appeared and rapidly spread worldwide and World Health Organization declared a pandemic on March 11, 2020. The roles and characteristics of coronavirus have captured much attention due to its power of causing a wide variety of infectious diseases, from mild to severe on humans. The detection of the lethality of human coronavirus is key to estimate the viral toxicity and provide perspective for treatment. We developed alignment-free machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of potential human-adapted coronavirus using genomic nucleotide. We performed extensive experiments through six different feature transformation and machine learning algorithms in combination with digital signal processing to infer the lethality of possible future novel coronaviruses using previous existing strains. The results tested on SARS-CoV, MERS-Cov and SARS-CoV-2 datasets show an average 96.7% prediction accuracy. We also provide preliminary analysis validating the effectiveness of our models through other human coronaviruses. Our study achieves high levels of prediction performance based on raw RNA sequences alone without genome annotations and specialized biological knowledge. The results demonstrate that, for any novel human coronavirus strains, this alignment-free machine learning-based approach can offer a reliable real-time estimation for its viral lethality.

bioinformatics↗

bioRxiv2020

Targeting heparan sulfate proteoglycan-assisted endocytosis as a COVID-19 therapeutic option

The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-CoV and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, facilitates the attachment of viral particles to the cell surface to promote cell entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry, and reveals drugs capable of targeting this important step in the viral life cycle.

cell biology↗

bioRxiv2020

RNF219 interacts with CCR4-NOT in regulating stem cell differentiation

Regulation of RNA stability plays a crucial role in gene expression control. Deadenylation is the initial rate-limiting step for the majority of RNA decay events. Here, we show that RING Finger Protein 219 (RNF219) interacts with the CCR4-NOT deadenylase complex. RNF219-CCR4-NOT exhibits deadenylation activity in vitro. RNA-seq analyses identify some of the 2-cell specific genes and the neuronal genes significantly down-regulated upon RNF219 knockdown, while up-regulated after depletion of the CCR4-NOT subunit CNOT10 in mouse embryonic stem (ES) cells. RNF219 depletion leads to impaired neuronal lineage commitment during ES cell differentiation. Our study suggests that RNF219 is a novel interacting partner of CCR4-NOT, and required for maintenance of ES cell pluripotency.View Full Text

molecular biology↗

bioRxiv2020

Nfkbid is required for immunity and antibody responses to Toxoplasma gondii

Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary infections in chronically infected mice. Here we report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection. To identify correlates of immunity, we utilized forward genetics to identify Nfkbid, a nuclear regulator of NF-{kappa}B that is required for B cell activation and B-1 cell development. Nfkbid-null mice (bumble) did not generate parasite-specific IgM and lacked robust parasite-specific IgG, which correlated with defects in B-2 cell maturation and class-switch recombination. Though high-affinity antibodies were B-2 derived, transfer of B-1 cells partially rescued the immunity defects observed in bumble mice and were required for 100% vaccine efficacy in bone marrow chimeric mice. Immunity in resistant mice correlated with robust isotype class-switching in both B cell lineages, which can be fine-tuned by Nfkbid gene expression. We propose a model whereby humoral immunity to T. gondii is regulated by Nfkbid and requires B-1 and B-2 cells for full protection. AUTHOR SUMMARYEukaryotic parasitic diseases account for approximately one fifth of all childhood deaths, yet no highly protective vaccine exists for any human parasite. More research must be done to discover how to elicit protective vaccine-induced immunity to parasitic pathogens. We used an unbiased genetic screen to find key genes responsible for immunity to the eukaryotic parasite Toxoplasma gondii. Our screen found Nfkbid, a transcription factor regulator, which controls B cell activation and innate-like B-1 cell development. Mice without Nfkbid were not protected against T. gondii and were deficient at making antibodies against the parasite. Our survival studies of vaccinated mice with and without B-1 compartments found that B-1 cells improved survival, suggesting that B-1 cells act in conjunction with B-2 cells to provide vaccine-induced immunity. Nfkbid and other loci identified in our unbiased screen represent potential targets for vaccines to elicit protective immune responses against parasitic pathogens.

immunology↗

bioRxiv2020

Adipose tissue macrophages orchestrate β cell adaptation in obesity through secreting miRNA-containing extracellular vesicles

Obesity induces an adaptive expansion of β cell mass and insulin secretion abnormality. Here, we explore a novel role of adipose tissue macrophages (ATMs) in mediating obesity-induced β cell function and proliferation through releasing miRNA-containing extracellular vesicles (EVs). ATM EVs derived from obese mice notably suppress insulin secretion in both in vivo and in vitro experiments, whereas there are more proliferating β cells in the islets treated with obese ATM EVs. Depletion of miRNAs blunts the ability of obese ATM EVs to regulate β cell responses. miR-155, a highly enriched miRNA within obese ATM EVs, exerts profound regulation on β cell functions, as evidenced by impaired insulin secretion and increased β cell proliferation after miR-155 overexpression in β cells. By contrast, knockout of miR-155 can attenuate the regulation of obese ATM EVs on β cell responses. We further demonstrate that the miR-155-Mafb axis plays a critical role in controlling β cell responses. Taken together, these studies show a novel mechanism by which ATM-derived EVs act as endocrine cargoes delivering miRNAs and subsequently mediating β cell adaptation and functional dysfunction in obesity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2020

DENV NS1 and MMP-9 cooperate to induce vascular leakage by altering endothelial cell adhesion and tight junction

Dengue virus (DENV) is a mosquito-borne pathogen that causes a spectrum of diseases including life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage is a common clinical crisis in DHF/DSS patients which is closely associated with increased endothelial permeability. The presence of vascular leakage causes hypotension, circulatory failure or disseminated intravascular coagulation as the disease progresses, which can lead to death under such conditions. However, the mechanisms by which DENV infection caused the vascular leakage are not fully understood. This study reveals a distinct mechanism by which DENV induces endothelial permeability and vascular leakage in human endothelial cells and mice tissues. We initially show that DENV2 promotes the matrix metalloproteinase-9 (MMP-9) expression and secretion in DHF patient serum, peripheral blood mononuclear cells (PBMCs) and macrophages, and further reveal that DENV non-structural protein 1 (NS1) induces MMP-9 expression through activating the nuclear factor {kappa}B (NF-{kappa}B) signaling pathway. Additionally, NS1 inhibits TIMP-1 expression to facilitates the MMP-9 enzymatic activity which alters the adhesion and tight junctions and vascular leakage in human endothelial cells and mouse tissues. Moreover, NS1 recruits MMP-9 to interact with {beta}-catenin and Zona occludins protein-1/2 to degrade the important adhesion and tight junction proteins, thereby inducing endothelial hyperpermeability and vascular leakage in human endothelial cells and mouse tissues. Thus, we reveal that DENV NS1 and MMP-9 cooperatively induce vascular leakage by impairing endothelial cell adhesion and tight junction, and suggest that MMP-9 may serve as a potential target for the treatment of hypovolemia in DSS/DHF patients. Author SummaryDENV is the most common mosquito-transmitted viral pathogen in humans. In general, DENV-infected patients are either asymptomatic or have flu-like symptoms with fever and rash. However, in severe cases of DENV infection, the disease may progress to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), the leading causes of morbidity and mortality in school-age children in tropical and subtropical regions. DENV-induced vascular leakage is characterized by enhanced vascular permeability without morphological damage to the capillary endothelium. We found that a distinct mechanism of DENV NS1 and MMP-9 cooperatively induce vascular leakage is the main reason leading to death in severe dengue patients. Also, NS1 recruits MMP-9 to degrade {beta}-catenin, ZO-1, ZO-2 to intervene endothelial hyperpermeability in human endothelial cells and mouse vascular. Finally, we reveal that DENV activating NF-{kappa}B signaling pathway induces MMP-9 expression, in patients, mice, PBMC and macrophages though the viral NS1 protein. This study would provide new in signs into the pathogenesis caused by DENV infection, and suggest that MMP-9 may acts as a drug target for the prevention and treatment of DENV-associated diseases.

microbiology↗

bioRxiv2020

Proteasome activator PA200 maintains stability of histone marks during transcription and aging

The epigenetic inheritance relies on stability of histone marks, but various diseases, including aging-related diseases, are usually associated with alterations of histone marks. How the stability of histone marks is maintained still remains unclear. The core histones can be degraded by the atypical proteasome, which contains the proteasome activator PA200, in an acetylation-dependent manner during somatic DNA damage response and spermiogenesis. Here we show that PA200 promotes the transcription-coupled degradation of the core histones, and plays an important role in maintaining the stability of histone marks. Degradation of the histone variant H3.3, which is incorporated into chromatin during transcription, was much faster than that of its canonical form H3.1, which is incorporated during DNA replication. This degradation of the core histones could be suppressed by the transcription inhibitor, the proteasome inhibitor or deletion of PA200. The histone deacetylase inhibitor accelerated the degradation rates of H3 in general, especially its variant H3.3, while the mutations of the putative acetyl-lysine-binding region of PA200 abolished histone degradation in the G1-arrested cells, supporting that acetylation is involved in the degradation of the core histones. Deletion of PA200 dramatically altered deposition of the active transcriptional hallmarks (H3K4me3 and H3K56ac) and transcription, especially during cellular aging. Furthermore, deletion of PA200 or its yeast ortholog Blm10 accelerated cellular aging. Notably, the PA200-deficient mice displayed a range of aging-related deteriorations, including immune malfunction, anxiety-like behaviors and shorter lifespan. Thus, the proteasome activator PA200 is critical to the maintenance of the stability of histone marks during transcription and aging.

cell biology↗

bioRxiv2020

The Forensic Landscape and the Population Genetic Analyses of Hainan Li Based on Massively Parallel Sequencing DNA Profiling

Due to the formation of the Qiongzhou Strait by climate change and marine transition, Hainan island isolated from the mainland southern China during the Last Glacial Maximum. Hainan island, located at the southernmost part of China and separated from the Leizhou Peninsula by the Qiongzhou Strait, laid on one of the modern human northward migration routes from Southeast Asia to East Asia. The Hlai-language speaking Li minority, the second largest population after Han Chinese in Hainan island, is the direct descendants of the initial migrants in Hainan island and has unique ethnic properties and derived characteristics, however, the forensic associated studies on Hainan Li population are still insufficient. Hence, 136 Hainan Li individuals were genotyped in this study using the MPS-based ForenSeq DNA Signature Prep Kit (DNA Primer Set A) to characterize the forensic genetic polymorphism landscape, and DNA profiles were obtained from 152 different molecular genetic markers (27 autosomal STRs, 24 Y-STRs, 7 X-STRs, and 94 iiSNPs). A total of 419 distinct length variants and 586 repeat sequence sub-variants, with 31 novel alleles (at 17 loci), were identified across the 58 STR loci from the DNA profiles of Hainan Li population. We evaluated the forensic characteristics and efficiencies of DAPA, it demonstrated that the STRs and iiSNPs in DAPA were highly polymorphic in Hainan Li population and could be employed in forensic applications. In addition, we set up three Datasets, which included the genetic data of (I). iiSNPs (27 populations, 2640 individuals), (II). Y-STRs (42 populations, 8281 individuals), and (III). Y-haplogroups (123 populations, 4837 individuals) along with the population ancestries and language families, to perform population genetic analyses separately from different perspectives. In conclusion, the phylogenetic analyses indicated that Hainan Li, with a southern East Asia origin and Tai-Kadai language-speaking language, is an isolated population relatively. But the genetic pool of Hainan Li influenced by the limited gene flows from other Tai-Kadai populations and Hainan populations. Furthermore, the establishment of isolated population models will be beneficial to clarify the exquisite population structures and develop specific genetic markers for subpopulations in forensic genetic fields.

genetics↗

bioRxiv2020

Lutein restores synaptic functionality in a C. elegans model for mitochondrial complex I deficiency

Complex I deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scarcity of appropriate model systems to study them. Caenorhabditis elegans is a genetically tractable model organism widely used to investigate neuronal pathologies. Here, we generated new C. elegans models for mitochondriopathies and showed that depletion of Complex I subunits recapitulates biochemical, cellular and neurodevelopmental aspects of the human diseases. Two models, nuo-5/NDUFS1- and lpd-5/NDUFS4-depleted animals, were exploited for a suppressor screening that identified lutein for its ability to rescue animals neurodevelopmental deficits. We uncovered overexpression of synaptic neuroligins as an evolutionarily conserved consequence of mitochondrial dysfunction, which we found to mediate an early cholinergic defect in C. elegans. We showed lutein exerts its beneficial effects by restoring neuroligin expression independently from its antioxidant activity, thus pointing to a possible novel pathogenetic target for the human disease.

neuroscience↗