A5002169807- Autoimmune Neurological Disorders and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Peripheral Neuropathies and Disorders
- Systemic Lupus Erythematosus Research
- Nerve injury and regeneration
- Amyotrophic Lateral Sclerosis Research
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Neurological Disorders and Treatments
- Prion Diseases and Protein Misfolding
- HIV Research and Treatment
- RNA regulation and disease
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Angiogenesis and VEGF in Cancer
- Cellular transport and secretion
- Acute Ischemic Stroke Management
- Transcranial Magnetic Stimulation Studies
- Calpain Protease Function and Regulation
- Cancer Immunotherapy and Biomarkers
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Spinal Cord Injury Research
- Cancer Cells and Metastasis
MRC Prion Unit
2023
University College London
2023
Medical Research Council
2023
University of Oxford
2018-2022
University of Otago
2016-2020
Brain Research New Zealand
2014-2020
John Radcliffe Hospital
2020
Institute of Neurological Sciences
2009-2014
National Research Council
2009-2014
University of Catania
2011
Introduction N‐methyl‐D‐aspartate receptor (NMDAR) antibody encephalitis is mediated by immunoglobulin G (IgG) autoantibodies directed against the NR1 subunit of NMDAR. Around 20% patients have an underlying ovarian teratoma, and condition responds to early immunotherapies teratoma removal. However, despite clear therapeutic relevance, mechanisms NR1‐IgG production contribution germinal center B cells levels are unknown. Methods Clinical data longitudinal paired serum NR1‐reactive IgM IgG...
Abstract Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) LGI1. We explore their sequences binding characteristics, plus pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, behavioural electrophysiological assessments vivo after mAb injections into the hippocampus. In live cell-based assays, LGI1 epitope recognition...
Significance By studying paired blood and deep cervical lymph node samples from patients with neuromyelitis optica spectrum disorders, our data provide evidence for a germinal center–based generation of aquaporin-4 antibodies. Frequent serum immunoglobulin Ms (IgMs) shifts in IgG subclasses were observed alongside preferential synthesis IgGs aquaporin-4–reactive B cells within nodes. Both intranodal antibodies robustly eliminated rituximab administration. This study systematically explores...
FRAXE is a form of mild to moderate mental retardation due the silencing FMR2 gene. The cellular function protein presently unknown. By analogy with its homologue AF4, was supposed have role in transcriptional regulation, but robust evidences supporting this hypothesis are lacking. We observed that co-localizes splicing factor SC35 nuclear speckles, regions where factors concentrated, assembled and modified. Similarly what reported for factors, blocking or transcription leads accumulation...
Abstract Although recovery following a stroke is limited, undamaged neurons under the right conditions can establish new connections and take on-board lost functions. Sonic hedgehog (Shh) signaling integral for developmental axon growth, but its role after injury has not been fully examined. To investigate effects of Shh on neuronal sprouting injury, we used an in vitro model glial scar, whereby cortical astrocytes were mechanically traumatized to mimic reactive astrogliosis observed stroke....
Abstract The extracellular matrix fragment perlecan domain V is neuroprotective and functionally restorative following experimental stroke. As neurogenesis an important component of chronic post-stroke repair, previous studies have implicated in developmental neurogenesis, we hypothesized that could a broad therapeutic window by enhancing after We demonstrated chronically increased the brains human stroke patients, suggesting it present during neurogenic periods. Furthermore, deficient mice...
This study aimed to characterise both neuronal autoantibodies and levels of interferon α, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) plasma from 35 patients with (SLE; 15 NPSLE) showed no antibodies against natively expressed N-methyl-D-aspartate receptors (NMDARs), or the surface live hippocampal neurons. By comparison controls (n = 104), SLE had that bound a peptide representing extracellular domain NMDARs (p < 0.0001),...
Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, impaired IGF-I signaling has been shown to play a role various neurological diseases including stroke. The aim present study was investigate efficacy an optimized variant by adding 40 kDa polyethylene glycol (PEG) chain form PEG-IGF-I. We show that PEG-IGF-I slower clearance which allows for twice-weekly dosing maintain steady-state serum levels mice. Using photothrombotic model focal stroke, from...
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Abstract The self-templating nature of prions plays a central role in prion pathogenesis and is associated with infectivity transmissibility. Since propagation proteopathic seeds has now been acknowledged principal pathogenic process many types dementia, more insight into the molecular mechanism replication vital to delineate specific common disease pathways. By employing highly discriminatory anti-PrP antibodies conversion-tolerant PrP chimera, we here report that de novo conversion...
Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable infectious in Western populations. We evaluated the frequency and significance AE neuronal autoantibodies comparison etiologies among patients presenting with a South Asian population.Ninety-nine consecutive clinical diagnosis encephalitis/meningoencephalitis admitted two largest tertiary-care hospitals Sri Lanka were studied. PCR ELISA used screen viruses while Gram stain culture bacteria. Sera tested...