A5007704496- Amyotrophic Lateral Sclerosis Research
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Hereditary Neurological Disorders
- Neurogenetic and Muscular Disorders Research
- Prion Diseases and Protein Misfolding
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Nerve injury and regeneration
- Muscle Physiology and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological diseases and metabolism
- Healthcare and Venom Research
- biodegradable polymer synthesis and properties
- Cholinesterase and Neurodegenerative Diseases
- thermodynamics and calorimetric analyses
- Inflammatory Myopathies and Dermatomyositis
- DNA Repair Mechanisms
- Neuroscience and Neuropharmacology Research
- Calpain Protease Function and Regulation
- Cardiomyopathy and Myosin Studies
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
University College London
2013-2023
National Hospital for Neurology and Neurosurgery
2013-2023
Ghent University Hospital
2018
Sobell House
2013-2018
MRC Prion Unit
2016-2018
Montreal Neurological Institute and Hospital
2018
Vita-Salute San Raffaele University
2018
Medical Research Council
2016
Cancer Research UK
2012
Gedeon Richter (Hungary)
2001
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motoneuron degeneration, resulting in muscle paralysis and death, typically within 1-5 years of diagnosis. Although the pathogenesis ALS remains unclear, there evidence for involvement proteasome dysfunction heat shock proteins disease. We have previously shown that treatment with co-inducer response called arimoclomol effective SOD(G93A) mouse model ALS, delaying disease progression extending...
Article15 May 2018Open Access Source DataTransparent process Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics amyotrophic lateral sclerosis Pietro Fratta Corresponding Author [email protected] orcid.org/0000-0002-8762-8188 UCL Institute Neurology, MRC Centre for Neuromuscular Disease, London, UK Search more papers by this author Prasanth Sivakumar Jack Humphrey Genetics Institute, Kitty Lo Thomas Ricketts Mammalian Unit, Harwell, Hugo Oliveira Jose...
Augmenting the heat shock response with arimoclomol ameliorates pathology in cellular and animal models of inclusion body myositis.
Mutations in FUS are causative for amyotrophic lateral sclerosis with a dominant mode of inheritance. In trying to model FUS-amyotrophic (ALS) mouse it is clear that dosage-sensitive and effects arise from overexpression per se transgenic strains. Novel models required maintain physiological levels expression recapitulate the human disease-with progressive loss motor neurons heterozygous animals. Here, we describe new humanized FUS-ALS frameshift mutation, which fulfils both criteria:...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically SOD1G93A mouse model ALS, proposed to play role neuron as well other pathologies nervous system, such Alzheimer's hereditary neuropathies. In this study, we screen library small-molecule kinase inhibitors towards identification pharmacological enhancers retrograde signalling endosomes, which...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results in the death of motor neurons brain and spinal cord. The generally strikes mid-life, relentlessly leading to paralysis death, typically 3-5 years after diagnosis. No effective treatments are available. Up 10% ALS familial, usually autosomal dominant. Several causative genes known and, these, mutant superoxide dismutase 1 (SOD1) by far most frequently found, accounting for up 20% familial ALS. A range...
Background Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterised by progressive degeneration of motor neurons leading to death, typically within 3–5 years symptom onset. The diagnosis ALS largely reliant on clinical assessment and electrophysiological findings. Neither specific investigative tools nor reliable biomarkers are currently available enable early or monitoring disease progression, hindering the design treatment trials. Methodology/Principal...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in spinal cord, brain stem, and cortex. Mutations superoxide dismutase (SOD1) are associated with familial ALS lead to SOD1 protein misfolding aggregation. Here we show that molecular chaperone, HSJ1 (DNAJB2), mutations which cause distal hereditary neuropathy, can reduce mutant aggregation improve neuron survival models ALS. Overexpression human HSJ1a (hHSJ1a) vivo...
Abstract Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness due to the progressive death rod and cone photoreceptors in retina. There are currently no effective treatments for RP. Inherited mutations rhodopsin, light-sensing protein photoreceptor cells, most common autosomal-dominant The majority including P23H substitution, lead misfolding, which feature many neurodegenerative disorders. Previous studies have shown upregulating molecular chaperone expression can...
Axonal transport is essential for neuronal function and survival. Defects in axonal have been identified as an early pathological feature several disorders of the nervous system. The visualisation quantitative analysis vivo rodent models neurological disease therefore crucial to improve our understanding pathogenesis identification novel therapeutics. Here, we describe a method imaging signalling endosomes sciatic nerve live, anaesthetised mice. This allows multiparametric, motor sensory...
Abstract Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, cellular autonomy uniformity of astrocyte reactive transformation in different genetic forms amyotrophic remain unresolved. Here we systematically examine these issues by using highly enriched human induced pluripotent stem cell-derived from patients with VCP SOD1 mutations. We show that mutant undergo cell-autonomous...
Abstract Pharmacological up-regulation of heat shock proteins (hsps) rescues motoneurons from cell death in a mouse model amyotrophic lateral sclerosis. However, the relationship between increased hsp expression and neuronal survival is not straightforward. Here we examined effects two pharmacological agents that induce response via activation HSF-1, on stressed primary culture. Although both arimoclomol celastrol induced Hsp70, their culture were significantly different. Whereas had...
Mutations in the small heat shock protein Hsp27, encoded by HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits implicated disease. In this study, we conducted analysis of bidirectional movements mitochondria primary neuron axons expressing wild mutant Hsp27. We found significantly slower retrograde Ser135Phe, Pro39Leu Arg140Gly Hsp27 neurons than neurons, although...
There are substantial differences across species in the organization and function of motor pathways. These extend to basic electrophysiological properties. Thus, rat cortex, pyramidal cells have long duration action potentials, while macaque, some neurons exhibit short "thin" spikes. may be related expression fast potassium channel Kv3.1b, which interneurons is associated with generation thin Rat typically lack these channels, there reports that they present macaque pyramids. Here we made a...
Hereditary sensory neuropathy type 1 (HSN-1) is a peripheral most frequently caused by mutations in the SPTLC1 or SPTLC2 genes, which code for two subunits of enzyme serine palmitoyltransferase (SPT). SPT catalyzes first step de novo sphingolipid synthesis. Mutations result change substrate specificity, causes production atypical deoxysphinganine and deoxymethylsphinganine, rather than normal product, sphinganine. Levels these abnormal compounds are elevated blood HSN-1 patients this thought...
Down Syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and results in a spectrum phenotypes including learning memory deficits, motor dysfunction. It has been hypothesized that an additional copy few Hsa21 dosage-sensitive genes causes these phenotypes, but this challenged observations aneuploidy can cause the mass action large numbers genes, with undetectable contributions from individual sequences. The abnormalities DS are relatively understudied-the identity causative mechanism...