A5024095075- Botulinum Toxin and Related Neurological Disorders
- Advanced biosensing and bioanalysis techniques
- Neurological disorders and treatments
- Nerve injury and regeneration
- Hereditary Neurological Disorders
- Molecular Junctions and Nanostructures
- Signaling Pathways in Disease
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- Parkinson's Disease Mechanisms and Treatments
- RNA Interference and Gene Delivery
- Molecular Communication and Nanonetworks
- RNA regulation and disease
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Pain Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Bacteriophages and microbial interactions
- Nanocluster Synthesis and Applications
- Photoreceptor and optogenetics research
- Insect and Pesticide Research
- Peripheral Neuropathies and Disorders
- Prion Diseases and Protein Misfolding
- Advanced Fluorescence Microscopy Techniques
- Traumatic Brain Injury and Neurovascular Disturbances
University College London
2016-2024
UK Dementia Research Institute
2021-2024
National Hospital for Neurology and Neurosurgery
2018-2024
University of Chicago
2015-2021
Tata Institute of Fundamental Research
2011-2013
National Centre for Biological Sciences
2011-2013
Abstract Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, is needed for neuronal development, function, survival. Deficits in axonal have been detected at pre-symptomatic stages the SOD1 G93A TDP-43 M337V mouse models amyotrophic lateral sclerosis (ALS), suggesting that impairments this critical process are fundamental disease pathogenesis. Strikingly, ALS, fast motor neurons (FMNs) degenerate first whereas slow (SMNs) more...
Abstract Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but not PNS damage, as it expressed throughout the and CNS. Peripherin, another intermediate filament protein, almost exclusively in axons. We postulated that peripherin be a promising biomarker damage. demonstrated distributed sciatic nerve, lesser extent spinal cord tissue...
DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more sequences by their self-assembly. Due to the molecularly programmable as well modular nature of DNA, such designer architectures have great potential for in cellulo and vivo applications. However, demonstrations functionality living systems necessitates a method assess stability relevant nanostructures. Here, we outline quantitatively assay lifetime various vivo. This exploits property...
Gain-of-function mutations in the housekeeping gene GARS1, which lead to expression of toxic versions glycyl-tRNA synthetase (GlyRS), cause selective motor and sensory pathology characterizing Charcot-Marie-Tooth disease (CMT). Aberrant interactions between GlyRS mutants different proteins, including neurotrophin receptor tropomyosin kinase B (TrkB), underlie CMT type 2D (CMT2D); however, our pathomechanistic understanding this untreatable peripheral neuropathy remains incomplete. Through...
Dystonia, a neurological disorder defined by abnormal postures and disorganized movements, is considered to be neural circuit with dysfunction arising within between multiple brain regions. Given that spinal circuits constitute the final pathway for motor control, we sought determine their contribution this movement disorder. Focusing on most common inherited form of dystonia in humans, DYT1- TOR1A , generated conditional knockout torsin family 1 member A ( Tor1a ) gene mouse cord dorsal...
Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest family genetically linked CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate type C (DI-CMTC) YARS1 driving toxic gain-of-function encoded tyrosyl-tRNA (TyrRS), mediated exposure of consensus neomorphic...
Abstract Tetanus neurotoxin (TeNT) causes spastic paralysis by inhibiting neurotransmission in spinal inhibitory interneurons. TeNT binds to the neuromuscular junction, leading its internalisation into motor neurons and subsequent transcytosis While extracellular matrix proteins nidogens are essential for binding, molecular composition of receptor complex remains unclear. Here, we show that receptor-type protein tyrosine phosphatases LAR PTPRδ interact with nidogen-TeNT complex, enabling...
Pathological tau aggregates propagate across functionally connected neuronal networks in human neurodegenerative pathologies, such as Alzheimer's disease. However, the mechanism underlying this process is poorly understood. Several studies have showed that release dependent on activity and pathological found extracellular space free form, well lumen of vesicles. We recently metabotropic glutamate receptor SNAP25 integrity modulate from mouse synaptosomes. Here, we leveraged botulinum...
Nucleic acid nanodevices present great potential as agents for logic-based therapeutic intervention well in basic biology. Often, however, the disease targets that need corrective action are localized specific organs, and thus realizing full of DNA also requires ways to target them cell types vivo. Here, we show by exploiting either endogenous or synthetic receptor-ligand interactions leveraging biological barriers presented organism, can extraneously introduced
Abstract Tetanus toxin is one of the most potent neurotoxins and causative agent tetanus. This neurotoxin binds to neuromuscular junction and, after internalisation into motor neurons, undergoes long-distance axonal transport transcytosis spinal cord inhibitory interneurons. Inside cytoplasm interneurons, catalytic chain blocks neurotransmitter release, leading spastic paralysis. Whilst effects tetanus intoxication have been extensively studied, molecular composition its receptor complex...
Abstract Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments neurons, is needed for neuronal development, function, survival. Deficits in axonal have been detected at pre-symptomatic stages mouse models amyotrophic lateral sclerosis (ALS), suggesting that impairments are fundamental disease pathogenesis. However, the precise mechanisms responsible deficits whether they preferentially affect α-motor neuron (MN) subtypes remain unresolved....
Abstract Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest family genetically linked CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate type C (DI-CMTC) YARS1 driving toxic gain-of-function encoded tyrosyl-tRNA (TyrRS), mediated exposure of consensus...
Abstract Pathological tau aggregates propagate across functionally connected neuronal networks in human neurodegenerative pathologies, such as Alzheimer’s disease. However, the mechanism underlying this process is poorly understood. Several studies have showed that release dependent on activity and pathological found extracellular space free form, well lumen of vesicles. We recently metabotropic glutamate receptor SNAP25 integrity modulate from mouse synaptosomes. Here, we leveraged...