ATP

Cytoskeletal connectors: Deciphering the fundamental mechanisms of cytoskeletal dynamics and transport

PROJECT SUMMARY The cytoskeleton is a dynamic network of filamentous structures, including microtubules and actin, that regulate essential cellular processes such as cell shape, growth, and signaling. Cytoskeleton also serves as tracks for molecular motors, which transport a variety of cellular cargoes, including organelles, macromolecules, and vesicles. These cargoes are linked to motors by specialized connector proteins. Disruptions in connector proteins are implicated in a range of neurodevelopmental and neurodegenerative diseases, as well as cancers. Despite their importance, these proteins continue to be understudied, primarily due to their perceived role as passive linkers and the technical challenges in working with them. However, recent discoveries suggest that connector proteins may play more active roles, in some cases even have enzymatic functions. This proposal aims to uncover mechanisms of connector protein functions through a detailed investigation of actin-microtubule and motor-cargo interactions. Actin and microtubules are linked by the spectraplakin family of large and evolutionarily conserved proteins, critical for neuronal development and differentiation. Recent discoveries of ATPase domains within these proteins suggest they may haves beyond simply linking cytoskeletal components. One goal of this proposal is to investigate the role of spectraplakin’s ATPase domains via structural, biochemical, and cell biology approaches. Another goal is to explore how dynamic changes in motor-cargo connectors facilitate the transport of diverse cargoes along microtubule tracks. The focus will be on the cytoplasmic dynein-1 (dynein) and the connectors (adaptors) that activate and link dynein to cargo. Dynein is a microtubule minus-end directed motor that plays essential roles in cell division, and transports hundreds of different cellular cargoes. While several motor-cargo connectors have been identified, the regulatory mechanisms enabling cargo transport are not fully understood. We are investigating whether connector proteins work together to activate dynein movement and/or facilitate cargo handoff between different dynein complexes. Using innovative approaches, including time- resolved cryo-EM, complex in-vitro reconstitutions, and live-cell imaging in induced neurons, we are uncovering critical mechanisms that govern cytoskeletal connector proteins, furthering our understanding of how the cytoskeleton regulates essential cellular processes.

Validating Causality of Disputed Mitochondrial Variants in Inborn Errors of Metabolism

PROJECT SUMMARY Primary mitochondrial disease (PMD) encompasses multi-systemic disorders caused by impaired mitochondrial function. PMDs arise from pathogenic variants in either nuclear genes encoding mitochondrial proteins, or in the mitochondrial DNA (mtDNA) genome. Clinical diagnosis is challenging due to phenotypic heterogeneity, underscoring the importance of genetic diagnosis. ACMG/AMP guidelines provide a well-established framework for interpreting nuclear DNA variants while diagnosing genetic diseases. Their application to mtDNA variants, however, remains challenging due to unique features of mtDNA: maternal inheritance, heteroplasmy, threshold effects, and effect of transfer or ribosomal RNA rather than coding variants. To address these challenges, the ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, co-chaired by the Multi-PIs of this study, developed widely adopted ACMG/AMP revised guidelines for mtDNA variant interpretation. Over the past five years, this global expert panel has curated more than 280 mtDNA variant. Because of the lack of functional data of individual mtDNA variants in the literature, 23 previously reported pathogenic (P) variants were classified as Variants of Uncertain Significance (VUS), hindering definitive PMD diagnoses and therapeutic development. This R01 project aims to resolve the pathogenicity of these 23 mtDNA VUS through functional validation, leveraging advanced mtDNA base editing and single-cell genomics in in vitro and in vivo models. In Aim 1, we will create human 143B cell line models for 20 VUS using cutting-edge mtDNA editing techniques, optimized for efficiency and minimal off-target effects. Single-cell genomics (mtscATAC-seq and scRNA-seq) will assess heteroplasmy and genomic changes, while functional assays will evaluate mitochondrial ATP production, oxidative phosphorylation, membrane potential, and redox stress. Aim 2 will develop zebrafish models for 17 conserved VUS, characterizing phenotypic and mitochondrial outcomes to corroborate in vitro findings and PMD patient phenotypes. This study will clarify longstanding uncertainties regarding the pathogenicity of these mtDNA VUSs which were nonetheless reported to be pathogenic with often strong genetic evidence but limited functional data. The study will also establish valuable cell and zebrafish models and provide mechanistic insights of PMDs. The resulting resources will be shared with the scientific community to accelerate research and therapeutic advancements for novel precision medicine approaches for PMDs.

Hepatotoxicity of Legacy and Replacement PFAS: Role of BRUCE-Mitochondrial Interactions

Epidemiological studies have shown a strong association between exposure to PFAS (Per- and Poly- fluoroalkyl Substances) and liver toxicity. Particularly, legacy C8-PFAS members, PFOS (perfluorooctane sulfonate) and PFOA (perfluorooctanoic acid), are highly toxic, with PFOS estimated to be approximately 10 times more toxic than PFOA in ecotoxicity models. Consequently, PFAS replacements such as GenX and PFBS are marketed as safe alternatives, although growing evidence indicates that these substitutes also exhibit toxic effects. Lab animal model studies have shown hepatotoxic effects of both legacy and replacement PFAS members, characterized by Metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe form Metabolic dysfunction- associated steatohepatitis (MASH), the two chronic liver diseases affecting an estimated 80-100 million Americans. The broader objective of this project is to understand the underlying mechanisms of PFAS hepatotoxicity in MASLD/MASH. In this context, our initial studies have shown that PFAS exposure of mice downregulates hepatic BRUCE, an autophagy inhibitor, resulting in development of MASLD in WT, and more severe MASLD and even progression to MASH in BRUCE liver-knockdown (BKO) mice. Using primary hepatocytes, we found PFAS-induced BRUCE reduction compromised mitochondrial (mt) functions (respiration, fatty acid oxidation/FAO, and ATP production) and suppressed mitophagy in WT and more so in BKO mice. Pharmacological restoration of mt function in mice prevented PFAS-induced MASLD/MASH. Guided by these compelling preliminary data and scientific premise, we hypothesize that PFAS degradation of BRUCE in hepatocytes induces excessive autophagy (resulting in cytotoxicity) and inhibits mitophagy (resulting in accumulation of damaged mitochondria), leading to release of mtDAMPs to activate inflammation/ fibrosis, thereby facilitating progression from MASLD to MASH. We will test this by three specific aims. Aim 1 (ex vivo) is to determine the human-relevant PFAS doses that modulate BRUCE levels for homeostatic vs cytotoxic autophagy and how BRUCE in turn regulates autophagy. Aim 2 (ex vivo) will investigate BRUCE-driven mitophagy pathway specific to PFAS exposure at human-relevant doses. Aim 3 (ex vivo and in vivo) will involve ex vivo simulation experiments to characterize the role of PFAS-induced, BRUCE-dependent hepatocyte- released mt DAMPs in activation of immune and fibrogenic cells using co-culture assays. Next, we will perform in vivo intervention to validate the role of PFAS-damaged mitochondria in driving MASH progression in mouse models. Furthermore, human relevance of the delineated mechanisms will be ascertained and validated using iPSC-derived human liver organoid system. Impact: This project will advance our understanding of autophagy/mitophagy-centric mechanisms with therapeutic potential in the context of PFAS-induced liver disease MASLD/MASH.

ATPase Chromatin Remodeling Complexes as Modulators of HIV-1 Latency and Therapeutic Targets

Abstract Significance: HIV persists in long-lived CD4⁺ T cell reservoirs despite suppressive ART, as integrated proviruses remain poised for reactivation. Chromatin remodeling is a central barrier to durable silencing, yet most studies have focused on SWI/SNF family members. The roles of non- SWI/SNF remodelers remain poorly defined, limiting our ability to rationally design host-directed “block-and-lock” cure strategies. Our unbiased shRNA screen of all 16 human remodeler ATPases identified EP400, CHD1, and CHD9 as repressors and INO80A, SMARCA5, and CHD2 as activators, establishing chromatin remodeling as a key determinant of HIV latency. Innovation: Our prior studies revealed that the p400 complex regulates HIV transcription through dual mechanisms: directly, by engaging Tat via the DMAP1 subunit to block Tat-TAR RNA interactions and restrict p-TEFb recruitment; and indirectly, by altering host transcriptional programs that control T cell activation states. Building on this mechanistic precedent and methodological platform, we now focus on INO80A, SMARCA5, CHD1, and CHD2, remodelers from distinct ATPase families that govern Tat-independent checkpoints at initiation, pause release, and elongation. Methodologically, we will apply TurboID-ChAP-MS (locus-specific proteomics), BEM-seq (single-nucleosome mapping), and degron-mediated acute depletion with ATPase-dead rescue to interrogate remodeler function with unprecedented resolution. Approach: Aim 1 will define the ATPase requirement and transcriptional checkpoints regulated by INO80A, SMARCA5, CHD1, and CHD2 using degron/CRISPR perturbations, ChIP-seq, nascent RNA profiling, and nucleosome mapping. Aim 2 will characterize remodeler-specific complexes and Tat dependence at the HIV promoter via TurboID proximity labeling integrated with chromatin affinity purification-mass spectrometry. Aim 3 will test combinatorial perturbations in Jurkat and primary CD4⁺ T cell latency models, including ART-suppressed donor cells, to identify synergistic “block-and-lock” strategies that enforce durable proviral silencing. Impact: By defining remodeler-specific mechanisms at discrete transcriptional checkpoints and leveraging their enzymatic, druggable activities, this work will establish chromatin remodeling as a therapeutic axis for durable HIV suppression and functional cure.

Programmed axon death: from animal models into human disease

Programmed axon death is a widespread and completely preventable mechanism in injury and disease. Mouse and Drosophila studies define a molecular pathway involving activation of SARM1 NA Dase and its prevention by NAD synthesising enzyme NMNAT2 . Loss of axonal NMNAT2 causes its substrate, NMN , to accumulate and activate SARM1 , driving loss of NAD and changes in ATP , ROS and calcium. Animal models caused by genetic mutation, toxins, viruses or metabolic defects can be alleviated by blocking programmed axon death, for example models of CMT1B , chemotherapy-induced peripheral neuropathy (CIPN), rabies and diabetic peripheral neuropathy (DPN). The perinatal lethality of NMNAT2 null mice is completely rescued, restoring a normal, healthy lifespan. Animal models lack the genetic and environmental diversity present in human populations and this is problematic for modelling gene-environment combinations, for example in CIPN and DPN , and identifying rare, pathogenic mutations. Instead, by testing human gene variants in WGS datasets for loss- and gain-of-function, we identified enrichment of rare SARM1 gain-of-function variants in sporadic ALS , despite previous negative findings in SOD1 transgenic mice. We have shown in mice that heterozygous SARM1 loss-of-function is protective from a range of axonal stresses and that naturally-occurring SARM1 loss-of-function alleles are present in human populations. This enables new approaches to identify disorders where blocking SARM1 may be therapeutically useful, and the existence of two dominant negative human variants in healthy adults is some of the best evidence available that drugs blocking SARM1 are likely to be safe. Further loss- and gain-of-function variants in SARM1 and NMNAT2 are being identified and used to extend and strengthen the evidence of association with neurological disorders. We aim to identify diseases, and specific patients, in whom SARM1 -blocking drugs are most likely to be effective.

How does the metabolically-expensive mammalian brain adapt to food scarcity?

Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. I addressed this in the visual cortex of awake mice using whole-cell recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. I found that food restriction reduced synaptic ATP usage by 29% through a decrease in AMPA receptor conductance. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.

Metabolic spikes: from rogue electrons to Parkinson's

Conventionally, neurons are thought to be cellular units that process synaptic inputs into synaptic spikes. However, it is well known that neurons can also spike spontaneously and display a rich repertoire of firing properties with no apparent functional relevance e.g. in in vitro cortical slice preparations. In this talk, I will propose a hypothesis according to which intrinsic excitability in neurons may be a survival mechanism to minimize toxic byproducts of the cell’s energy metabolism. In neurons, this toxicity can arise when mitochondrial ATP production stalls due to limited ADP. Under these conditions, electrons deviate from the electron transport chain to produce reactive oxygen species, disrupting many cellular processes and challenging cell survival. To mitigate this, neurons may engage in ADP-producing metabolic spikes. I will explore the validity of this hypothesis using computational models that illustrate the implications of synaptic and metabolic spiking, especially in the context of substantia nigra pars compacta dopaminergic neurons and their degeneration in Parkinson's disease.

Neocortex saves energy by reducing coding precision during food scarcity

Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. We addressed this in the visual cortex of awake mice using whole-cell patch clamp recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. We found that food restriction resulted in energy savings through a decrease in AMPA receptor conductance, reducing synaptic ATP usage by 29%. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in orientation tuning and impaired fine visual discrimination. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.

Causal coupling between neural activity, metabolism, and behavior across the Drosophila brain

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioral states in many species, including worms, flies, fish, mice and humans. These global patterns alter energy metabolism in the brain over seconds to hours, making oxygen consumption and glucose uptake widely used proxies of neural activity. However, whether changes in neural activity are causally related to changes in metabolic flux in intact circuits on the sub-second timescales associated with behavior, is unclear. Moreover, it is unclear whether differences between rest and action are associated with spatiotemporally structured changes in neuronal energy metabolism at the subcellular level. My work combines two-photon microscopy across the fruit fly brain with sensors that allow simultaneous measurements of neural activity and metabolic flux, across both resting and active behavioral states. It demonstrates that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across large-scale brain networks. Further, using local optogenetic perturbation, I show that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, suggesting that neuronal metabolism predictively allocates resources to meet the energy demands of future neural activity. Finally, these studies reveal that the initiation of even minimal behavioral movements causes large-scale changes in the pattern of neural activity and energy metabolism, revealing unexpectedly widespread engagement of the central brain.

When spontaneous waves meet angiogenesis: a case study from the neonatal retina

By continuously producing electrical signals, neurones are amongst the most energy-demanding cells in the organism. Resting ionic levels are restored via metabolic pumps that receive the necessary energy from oxygen supplied by blood vessels. Intense spontaneous neural activity is omnipresent in the developing CNS. It occurs during short, well-defined periods that coincide precisely with the timing of angiogenesis. Such coincidence cannot be random; there must be a universal mechanism triggering spontaneous activity concurrently with blood vessels invading neural territories for the first time. However, surprisingly little is known about the role of neural activity per se in guiding angiogenesis. Part of the reason is that it is challenging to study developing neurovascular networks in tri-dimensional space in the brain. We investigate these questions in the neonatal mouse retina, where blood vessels are much easier to visualise because they initially grow in a plane, while waves of spontaneous neural activity (spreading via cholinergic starburst amacrine cells) sweep across the retinal ganglion cell layer, in close juxtaposition with the growing vasculature. Blood vessels reach the periphery by postnatal day (P) 7-8, shortly before the cholinergic waves disappear (at P10). We discovered transient clusters of auto-fluorescent cells that form an annulus around the optic disc, gradually expanding to the periphery, which they reach at the same time as the growing blood vessels. Remarkably, these cells appear locked to the frontline of the growing vasculature. Moreover, by recording waves with a large-scale multielectrode array that enables us to visualise them at pan-retinal level, we found that their initiation points are not random; they follow a developmental centre-to-periphery pattern similar to the clusters and blood vessels. The density of growing blood vessels is higher in cluster areas than in-between clusters at matching eccentricity. The cluster cells appear to be phagocytosed by microglia. Blocking Pannexin1 (PANX1) hemichannels activity with probenecid completely blocks the spontaneous waves and results in the disappearance of the fluorescent cell clusters. We suggest that these transient cells are specialised, hyperactive neurones that form spontaneous activity hotspots, thereby triggering retinal waves through the release of ATP via PANX1 hemichannels. These activity hotspots attract new blood vessels to enhance local oxygen supply. Signalling through PANX1 attracts microglia that establish contact with these cells, eventually eliminating them once blood vessels have reached their vicinity. The auto-fluorescence that characterises the cell clusters may develop only once the process of microglial phagocytosis is initiated.

Carnosine negatively modulates pro-oxidant activities of M1 peripheral macrophages and prevents neuroinflammation induced by amyloid-β in microglial cells

Carnosine is a natural dipeptide widely distributed in mammalian tissues and exists at particularly high concentrations in skeletal and cardiac muscles and brain. A growing body of evidence shows that carnosine is involved in many cellular defense mechanisms against oxidative stress, including inhibition of amyloid-β (Aβ) aggregation, modulation of nitric oxide (NO) metabolism, and scavenging both reactive nitrogen and oxygen species. Different types of cells are involved in the innate immune response, with macrophage cells representing those primarily activated, especially under different diseases characterized by oxidative stress and systemic inflammation such as depression and cardiovascular disorders. Microglia, the tissue-resident macrophages of the brain, are emerging as a central player in regulating key pathways in central nervous system inflammation; with specific regard to Alzheimer’s disease (AD) these cells exert a dual role: on one hand promoting the clearance of Aβ via phagocytosis, on the other hand increasing neuroinflammation through the secretion of inflammatory mediators and free radicals. The activity of carnosine was tested in an in vitro model of macrophage activation (M1) (RAW 264.7 cells stimulated with LPS + IFN-γ) and in a well-validated model of Aβ-induced neuroinflammation (BV-2 microglia treated with Aβ oligomers). An ample set of techniques/assays including MTT assay, trypan blue exclusion test, high performance liquid chromatography, high-throughput real-time PCR, western blot, atomic force microscopy, microchip electrophoresis coupled to laser-induced fluorescence, and ELISA aimed to evaluate the antioxidant and anti-inflammatory activities of carnosine was employed. In our experimental model of macrophage activation (M1), therapeutic concentrations of carnosine exerted the following effects: 1) an increased degradation rate of NO into its non-toxic end-products nitrite and nitrate; 2) the amelioration of the macrophage energy state, by restoring nucleoside triphosphates and counterbalancing the changes in ATP/ADP, NAD+/NADH and NADP+/NADPH ratio obtained by LPS + IFN-γ induction; 3) a reduced expression of pro-oxidant enzymes (NADPH oxidase, Cyclooxygenase-2) and of the lipid peroxidation product malondialdehyde; 4) the rescue of antioxidant enzymes expression (Glutathione peroxidase 1, Superoxide dismutase 2, Catalase); 5) an increased synthesis of transforming growth factor-β1 (TGF-β1) combined with the negative modulation of interleukines 1β and 6 (IL-1β and IL-6), and 6) the induction of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1). In our experimental model of Aβ-induced neuroinflammation, carnosine: 1) prevented cell death in BV-2 cells challenged with Aβ oligomers; 2) lowered oxidative stress by decreasing the expression of inducible nitric oxide synthase and NADPH oxidase, and the concentrations of nitric oxide and superoxide anion; 3) decreased the secretion of pro-inflammatory cytokines such as IL-1β simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1; 4) prevented Aβ-induced neurodegeneration in primary mixed neuronal cultures challenged with Aβ oligomers and these neuroprotective effects was completely abolished by SB431542, a selective inhibitor of type-1 TGF-β receptor. Overall, our data suggest a novel multimodal mechanism of action of carnosine underlying its protective effects in macrophages and microglia and the therapeutic potential of this dipeptide in counteracting pro-oxidant and pro-inflammatory phenomena observed in different disorders characterized by elevated levels of oxidative stress and inflammation such as depression, cardiovascular disorders, and Alzheimer’s disease.

On the purpose and origin of spontaneous neural activity

Spontaneous firing, observed in many neurons, is often attributed to ion channel or network level noise. Cortical cells during slow wave sleep exhibit transitions between so called Up and Down states. In this sleep state, with limited sensory stimuli, neurons fire in the Up state. Spontaneous firing is also observed in slices of cholinergic interneurons, cerebellar Purkinje cells and even brainstem inspiratory neurons. In such in vitro preparations, where the functional relevance is long lost, neurons continue to display a rich repertoire of firing properties. It is perplexing that these neurons, instead of saving their energy during information downtime and functional irrelevance, are eager to fire. We propose that spontaneous firing is not a chance event but instead, a vital activity for the well-being of a neuron. We postulate that neurons, in anticipation of synaptic inputs, keep their ATP levels at maximum. As recovery from inputs requires most of the energy resources, neurons are ATP surplus and ADP scarce during synaptic quiescence. With ADP as the rate-limiting step, ATP production stalls in the mitochondria when ADP is low. This leads to toxic Reactive Oxygen Species (ROS) formation, which are known to disrupt many cellular processes. We hypothesize that spontaneous firing occurs at these conditions - as a release valve to spend energy and to restore ATP production, shielding the neuron against ROS. By linking a mitochondrial metabolism model to a conductance-based neuron model, we show that spontaneous firing depends on baseline ATP usage and on ATP-cost-per-spike. From our model, emerges a mitochondrial mediated homeostatic mechanism that provides a recipe for different firing patterns. Our findings, though mostly affecting intracellular dynamics, may have large knock-on effects on the nature of neural coding. Hitherto it has been thought that the neural code is optimised for energy minimisation, but this may be true only when neurons do not experience synaptic quiescence.

Electrogenic Na+/K+-ATPases constrain excitable cell activity and pose additional evolutionary pressure

Bernstein Conference 2024

Neuronal bursting from an interplay of fast voltage and slow concentration dynamics mediated by the Na+/K+-ATPase

Bernstein Conference 2024

Association between adenosine A2A receptors and connexin 43 modulates hemichannels activity and ATP release in astrocytes exposed to amyloid-β peptides

Astrocytic GLUT1 ablation improves systemic glucose metabolism and preserves memory through enhanced insulin-stimulated ATP release

ATP6V1A, a key player for lysosomal function and autophagy process, is required for neuronal development and synaptic plasticity

Cortical pyramidal cells express thyroid hormone transporters MCT8 and OATP1C1 in human and monkey brain

The deafness causing pitch and audio-1 mutations affect the neuroplastin and plasma membrane Ca2+ ATPase complex function

K-ATP channels link mitochondrial (dys)function to neuronal excitability in the nucleus accumbens

Lipid environment is essential for optimal activity of Plasma membrane Ca2+ ATPase in murine brain tissue

Novel c.1799GC>G (p.P600R) substitution in ATP1A1 causes Demyelinating Charcot-Marie-Tooth in a Cypriot Patient

Plasma membrane Ca2+ ATPase 1 as a candidate to mediate the degeneration of dopaminergic neurons by inflammation in Parkinson’s disease

Spatiotemporal ATP release in cortical astrocytes

ATP stimulation regulates astrocyte-derived extracellular vesicle secretion and miRNA content

TBC1D24 interacts with v-ATPase and regulates pH homeostasis and autophagy in neurons

Thyroid hormone transporters MCT8 and OATP1C1 are expressed in neurons in the human and monkey basal ganglia and motor thalamus

Altered cell membrane ganglioside composition affects enzyme activity, expression, and submembrane localization of Na+,K+-ATPase in mouse brain

FENS Forum 2024

ATP6V1A is required for synaptic rearrangement and plasticity in murine hippocampal neurons

FENS Forum 2024

ATP8A2 controls phosphatidylserine externalisation, structural integrity, and survival in neurons

FENS Forum 2024

Cerebellar neurodegeneration in phospholipid flippases ATP8A1/ATP8A2 double knock-out mice can be ameliorated by inactivating a microglial PS receptor

FENS Forum 2024

Changes in neurotransmitter ATP/adenosine dynamics in the pathogenesis of metabolic liver diseases

FENS Forum 2024

Clinical and molecular characterization of ATP1A1-related Charcot-Marie-Tooth disease

FENS Forum 2024

The effect of altered ganglioside composition on leptin receptor and Na⁺,K⁺-ATPase in mouse thalamus

FENS Forum 2024

From systems biology to drug targets: ATP synthase subunit upregulation causes mitochondrial dysfunction in Shank3Δ4-22 mouse model of autism

FENS Forum 2024

Investigating the acute impact of sweeteners sucralose and Ace-K on ATP production and mitochondrial respiration in the hypothalamic GT1-7 cell line challenged with increased glucose

FENS Forum 2024

Mathematical modelling of ATP-induced Ca2+ transients in Deiters cells considering the tonotopic axis

FENS Forum 2024

Microglia modulate complex neuronal networks in acute brain slices despite their rapid, ATP-related phenotypic transformation

FENS Forum 2024

The regulatory impact of the BRG1 ATPase of SWI/SNF chromatin remodeling complex on seizure development

FENS Forum 2024

The repercussions of electrogenic Na+/K+-ATPase in excitable cells with high and variable firing rates

FENS Forum 2024

Simple mathematical model for replicating the ATP-induced Ca2+ transients in different types of cochlear supporting cells

FENS Forum 2024