Center for Neurosciences

Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by the alpha-synuclein protein pathology, which may be associated with a changed expression of the SNCA gene encoding this protein. We studied the expression of four SNCA transcript variants, encoding the protein isoforms SNCA-140, SNCA-126, SNCA-112, and SNCA-98, in blood leukocytes of 86 PD and 52 MSA patients compared to 50 control subjects without neurological pathology. All SNCA transcript variants were increased in leukocytes in MSA patients (predominantly alternatively spliced short transcripts), especially with parkinsonian type of disease. No significant SNCA expression changes were found in the group of PD patients. The results obtained emphasize the differences in the pathogenesis of these two synucleinopathies—PD and MSA.

Peripheral nerve injury can result in potentially devastating neurological deficits and often disproportionately impacts young workers. Recovery of motor function after peripheral nerve injury requires the regeneration of the nerve from the site of injury to the neuromuscular junction (NMJ), where signals must be transduced effectively across the synapse, resulting in target muscle contraction. For reasons that are not fully understood, after about 18 months of denervation, functional NMJs fail to recapitulate. This, in combination with the slow velocity of axon regeneration, significantly limits both the window of opportunity for intervention and surgical reconstruction options. Here, we review what is currently known with respect to NMJ physiology, anatomy, development, and changes after injury. We also highlight knowledge gaps and opportunities for study with the goal of developing novel, NMJ-focused avenues of treatment for patients after peripheral nerve injury.

The management of patients with acute vestibular vertigo (AVV) remains a difficult and pressing problem in modern medicine due to the variety of aetiological factors, the subjective nature of patient complaints, and the insufficient application of existing neurovestibular diagnostic algorithms in real clinical practice. Despite the large number of publications on the management of patients with AVV, certain issues regarding the examination and routing of patients remain unresolved to this day. Approximately a quarter of conditions manifested by AVV are caused by stroke or other life-threatening diseases, therefore emergency diagnosis is always necessary. Due to the insufficient informativeness of neuroimaging methods in patients with isolated vestibular vertigo, clinical diagnosis comes to the fore, requiring special training from doctors. Patients with peripheral causes of acute vestibular syndrome and vestibular migraine often do not receive fully effective treatment and recommendations for further rehabilitation in neurological hospitals, which makes an initially benign cause a trigger for chronic complaints of vertigo, leading to various functional disorders that slow down recovery, cause disability, and significantly reduce patients' quality of life. On 22 November 2025, a council of experts was held to discuss important issues related to the diagnosis, management and rehabilitation of patients with AVV, resulting in a proposed strategy for patient management.

The synaptic plasticity mechanisms that are thought to underlie learning and memory require Ca2+ influx mediated by N-methyl-D-aspartate receptors composed of glycine-binding GluN1 and glutamate-binding GluN2 subunits. Calmodulin (CaM) binding to the cytosolic regions in both GluN1 (residues 841-865, called GluN1-C0) and GluN2A (residues 1004-1023, called GluN2A-C0) may be important for Ca2+-dependent channel desensitization (CDD). Here, we report NMR, ITC and electrophysiological experiments to probe the structure and functional role of Ca2+-bound CaM (Ca2+-CaM) binding to both GluN1 and GluN2A subunits. Our ITC studies show that the GluN1-C0 peptide binds to both the N-lobe and C-lobe of Ca2+-CaM, whereas the GluN2A-C0 peptide binds to only the Ca2+-CaM C-lobe. Our NMR analysis reveals GluN2A residues (W1014 and V1018) interact with exposed hydrophobic residues in the Ca2+-CaM C-lobe. The NMR structure of Ca2+-CaM bound to the GluN1-C0 peptide indicates the two CaM lobes bind to opposite sides of the GluN1-C0 helix (C-lobe contacts M848, F852, A853 and N-lobe contacts A854, V855, W858). The GluN1 mutant F852E and the GluN2A mutant W1014E both perturbed CaM binding in ITC studies, and also diminished electrophysiologically-measured CDD, suggesting CaM interaction with these residues contributes to CDD. We propose a structural mechanism of CDD wherein channel desensitization is caused by the binding of four CaM per N-methyl-D-aspartate receptor subunit tetramer.

Abstract Functional optical imaging in nonhuman primates provides an important complement to electrophysiological approaches in neuroscience research, but its broader use has been limited by challenges in achieving large-scale, homogeneous expression of genetically encoded reporters, and imaging accessibility in species with gyrencephalic brains with sulci and fissures (e.g., rhesus macaques). Specifically, conventional local intracortical viral injections are invasive and often produce spatially restricted or heterogeneous expression, constraining population-level analyses. Here, we show that systemic intravenous delivery of an adeno-associated virus (AAV) capsid engineered for enhanced blood-brain barrier crossing, AAV.CAP-B10, supports robust and widespread expression of a calcium indicator CAaMP8s in the common marmoset. Intravenous delivery in two marmosets resulted in widespread cortical expression. Using a large cranial window over extrastriate visual area MT (and its satellite areas), we performed widefield single-photon imaging and two-photon cellular-resolution imaging in awake,behaving marmosets to functionally validate activity in this well studied primate visual-motion sensitive cortical area. Population level responses to visual motion and spatial organization measured with widefield imaging, as well as single-cell level motion direction tuning measured with two-photon imaging, were consistent with canonical properties of MT reported in previous electrophysiological studies. Quantitative analyses of lightsheet imaging after whole hemisphere brain clearing further confirmed the broad expression of GCaMP in both cortical and subcortical areas. Together, these results indicate that systemic delivery using AAV.CAP-B10 provides a minimally invasive approach for robust multi-scale functional optical imaging in awake, behaving marmosets.

Currently, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered promising drugs for the treatment of Alzheimer's disease (AD) and other neurodegenerative diseases due to their complex mechanism of action, which includes (in addition to general somatic effects) an impact on neuroplasticity. This necessitates a detailed study of drugs in this group using appropriate informative experimental models. Objective: to characterise the effect of semaglutide, one of the main representatives of the GLP-1RAs class, on the development of neurodegenerative processes in the hippocampus and cognitive impairments in animals with a streptozocin (STZ) model of AD. Material and methods . Streptozocin at a dose of 3 mg/kg was administered into the lateral ventricles of Wistar rats, and semaglutide at a dose of 0.1 mg/kg was administered intraperitoneally (every other day for 5 weeks). The behaviour of the animals was assessed in the ‘Novel Object Recognition’ and ‘T-Maze’ tests. Nine weeks after discontinuation of the drug, immunomorphological methods were used to determine the effect of semaglutide on neurodegenerative processes in the CA3 field of the hippocampus. Results. Streptozocin caused impaired recognition of a new object and increased the latency period for entering the closed arm of the T-maze, as well as leading to tau protein accumulation and mitochondrial and synaptic abnormalities in the CA3 field of the hippocampus. Semaglutide significantly attenuated streptozocin-induced memory impairment and depression-like behaviour and improved morphological indicators of synaptic integrity (based on the detection of synaptophysin and PSD95 proteins) neuronal energy metabolism (as determined by the detection of glycolysis and oxidative phosphorylation enzymes), and reduced tau protein phosphorylation. Conclusion . In a model of sporadic AD, semaglutide has been shown to attenuate cognitive impairment in laboratory animals and reduce the severity of morphological abnormalities in the CA3 region of the hippocampus, with the neuroprotective effect of the drug persisting after discontinuation of therapy.

ABSTRACTSpatial omics technologies enable high‐resolution mapping of transcriptomic, proteomic, and metabolic profiles within intact tissues, revealing how immune, stromal, and parenchymal cells interact in situ during inflammation. Chronic inflammation in skeletal muscle and the central nervous system is spatially organized within defined niches that shape disease progression and therapeutic response. In skeletal muscle, spatial analyses have uncovered fiber‐type‐specific vulnerability, regenerative trajectories, and immune–stromal crosstalk in disorders such as Duchenne muscular dystrophy and inclusion body myositis. In the central nervous system, these approaches have revealed compartmentalized neuroinflammation in multiple sclerosis, innate immune activation in amyotrophic lateral sclerosis, and immune evasion in glioma. Integration with single‐cell gene expression enables inference of cell–cell communication networks and identification of spatial gradients of immune activation and tissue remodeling. Despite major advances, clinical translation remains limited by small cohorts, methodological variability, and insufficient functional validation. As spatial profiling becomes more accessible, standardized, and scalable, it promises to stratify inflammatory disease states, identify tissue‐resident immune programs, and guide mechanism‐based therapies. Hence, spatial omics provide an unprecedented opportunity to resolve the cellular architecture of inflammation, revealing not only where immune activity occurs, but how it is orchestrated within complex tissue microenvironments.

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1235:"<h3></h3> MINORE (NCT04998812) is a prospective Phase IV, open-label study measuring ocrelizumab placental transfer, infant B-cell levels and detailed maternal and infant clinical outcomes, humoral immunity and safety. Thirty-five women were enrolled, 32 of whom received ocrelizumab within 6 months before last menstrual period (LMP) (3–6 months before LMP, n=18; and 0–3 months before LMP, n=14), and three women received ocrelizumab in the first trimester. The primary endpoint was the proportion of infants with B-cell levels below the lower limit of normal (LLN), measured at week 6 (W6) of life. All 35 pregnancies resulted in full-term live births. Ocrelizumab was undetectable in most infants, both in the umbilical cord blood at birth (94.3%, 33/35) and serum at W6 of life (97.0%, 32/33). All infant B-cell levels were above the age-specific LLN at W6 (100%, 34/34). Rates and types of adverse events (AEs) in mothers were in line with expected AEs during pregnancy, delivery, postpartum and infancy. Results of this study indicate that pregnancy planning is compatible with ocrelizumab treatment and support treatment decisions by clinicians and women with MS. ruth.dobson{at}qmul.ac.uk ";}

Abstract Crossing the blood-brain barrier (BBB) remains an unsolved challenge in neuro-oncology. Despite advances in glioblastoma biology, drug delivery into brain parenchyma is still limited by the inability to efficiently and selectively target tumor tissue. The next generation of therapies will require molecules that not only cross the BBB but do so with precision, persistence, and purpose. Small-format biologics like nanobodies, scFvs, Fabs, and mini-proteins offer distinct advantages in size, modularity, and BBB permeability, especially when conjugated with carrier molecules known to facilitate barrier translocation. But therapeutic success hinges on a narrow kinetic sweet spot: high-affinity binding to promote retention, yet reversible enough to release payloads effectively. With AI accelerating the design phase, experimental validation is now the bottleneck. We close this gap with SPOC (Sensor-integrated Proteome on Chip), a rapid, high-throughput biosensor platform that enables on-chip synthesis and real-time kinetic analysis of thousands of candidate binders. Using cell-free synthesis directly on surface plasmon resonance (SPR) chip, SPOC delivers high-resolution measurements of binding kinetics (on-rate, off-rate, residence time, and affinity) at scale. We applied SPOC to screen a panel of biologics targeting EGFR and HER2. This included engineered HER2-binding nanobody (VHH) variants, scFvs, and de novo AI-designed scaffolds. Resulting kinetic fingerprints allowed us to rapidly triage lead molecules with ideal BBB-targeting profiles. Building on these hits, we are developing BBB-penetrant drug conjugates by fusing the selected binders with chlorotoxin, a glioma-homing peptide from Leiurus quinquestriatus venom. Preliminary data demonstrate strong receptor engagement, promising residence times, and potential for selective tumor targeting in brain. SPOC is a novel and disruptive platform for neuro-oncology drug development—enabling rapid, parallelized optimization of biologics designed to breach the BBB and home in on brain tumors. We present new kinetic and functional data supporting its utility in accelerating the pipeline of next-generation targeted therapies.