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  • TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation.

    24 October 2018

    BACKGROUND: Mutations in the gene encoding TDP-43 have been identified in both familial and sporadic amyotrophic lateral sclerosis (ALS). METHODS: A mutation screen and copy number analysis in a motor neuron disease clinic cohort was conducted to characterise the genetic contribution of TARDBP. RESULTS: A novel missense mutation in a highly conserved region of TDP-43 was identified in a patient with sporadic ALS. The mutation is in close vicinity to previously identified changes. Copy number variation abnormalities were not detected. CONCLUSIONS: The findings stress the importance of TDP-43 in the pathogenesis of sporadic ALS.

  • The molecular genetics of non-ALS motor neuron diseases.

    24 October 2018

    Hereditary disorders of voluntary motor neurons are individually relatively uncommon, but have the potential to provide significant insights into motor neuron function in general and into the mechanisms underlying the more common form of sporadic Amyotrophic Lateral Sclerosis. Recently, mutations in a number of novel genes have been associated with Lower Motor Neuron (HSPB1, HSPB8, GARS, Dynactin), Upper Motor Neuron (Spastin, Atlastin, Paraplegin, HSP60, KIF5A, NIPA1) or mixed ALS-like phenotypes (Alsin, Senataxin, VAPB, BSCL2). In comparison to sporadic ALS these conditions are usually associated with slow progression, but as experience increases, a wide variation in clinical phenotype has become apparent. At the molecular level common themes are emerging that point to areas of specific vulnerability for motor neurons such as axonal transport, endosomal trafficking and RNA processing. We review the clinical and molecular features of this diverse group of genetically determined conditions and consider the implications for the broad group of motor neuron diseases in general.

  • Spinal muscular atrophies reveal motor neuron vulnerability to defects in ribonucleoprotein handling.

    24 October 2018

    PURPOSE OF REVIEW: Many forms of spinal muscular atrophy, a pure lower motor neuron disease, have been characterized clinically but the molecular basis of most of these is unknown. In this article we review recent developments in our understanding of the spinal muscular atrophies and how this knowledge has revealed important new insights into the causes of motor neuron vulnerability which may ultimately lead to novel therapies for this untreatable group of disorders. RECENT FINDINGS: The identification of the genetic basis of two forms of autosomal recessive spinal muscular atrophy has revealed that lower motor neurons appear to have a specific vulnerability to defects in RNA metabolism. Most notably, the survival motor neuron protein, deficient in the most common form of spinal muscular atrophy, plays a multifunctional role in ribonucleoprotein metabolism and pre-messenger RNA splicing. The role of this protein in motor neurons is currently under intense study. The identification of two other spinal muscular atrophy-causing genes has provided support for the central role of components of the RNA metabolic pathway in determining motor neuron survival. SUMMARY: Understanding the molecular basis of lower motor neuron vulnerability in disorders such as spinal muscular atrophy will ultimately allow these disabling disorders to be treated. In addition we can expect to learn much about basic neuronal biology and about the pathways that are relevant to more common neurodegenerative disorders such as amyotrophic lateral sclerosis.

  • Motor neurone disease.

    24 October 2018

    Motor neurone disease (MND), or amyotrophic lateral sclerosis (ALS), is a neurodegenerative disorder of unknown aetiology. Progressive motor weakness and bulbar dysfunction lead to premature death, usually from respiratory failure. Confirming the diagnosis may initially be difficult until the full clinical features are manifest. For all forms of the disease there is a significant differential diagnosis to consider, including treatable conditions, and therefore specialist neurological opinion should always be sought. Clear genetic inheritance has been demonstrated in a minority of patients with familial ALS but elucidation of the biological basis of genetic subtypes is also providing important information which may lead to treatments for sporadic forms of the disease. In the absence of curative or disease modifying therapy, management is supportive and requires a multidisciplinary approach. If, as seems likely, complex inherited and environmental factors contribute to the pathogenesis of MND, future treatment may involve a combination of molecular based treatments or restoration of cellular integrity using stem cell grafts.

  • Neurodegeneration and Inflammation Research Group

    15 January 2013

    DCN

    We explore the neuropathology of multiple sclerosis and other inflammatory and neurodegenerative diseases using a multidisciplinary team approach to post-mortem brain and spinal cord tissue. The aim is that the understanding derived from these studies will translate into ideas for improved treatments for living patients.

  • Experimental Neurology

    15 January 2013

    DCN

    Our goal is to define how activity in large populations of neurons is coordinated in healthy movement and how such coordination may go awry in diseases, translating this information in to improved treatment for Parkinson’s Disease and other disorders of movement.

  • Neuromuscular Disorders

    15 January 2013

    DCN

    We work to translate an understanding of the molecular mechanisms of disease at the neuromuscular synapse into treatments. Our work led us to be commissioned to provide a National Advisory and Diagnostic Service for congenital myasthenic syndromes.

  • Neural Injury Group

    19 February 2013

    DCN

    Our aim is to gain a better understanding of the response of the peripheral nervous system to injury in order to develop strategies to promote peripheral nerve repair and to prevent the development of neuropathic pain. To do this we employ a variety of multi-disciplinary techniques ranging from transgenic models to human psychophysical studies and genetics.

  • Pain, Palliative and Supportive Care (PaPaS) Review Group

    15 January 2013

    NDA

    The Cochrane Pain, Palliative and Supportive Care (PaPaS) Review Group is based at the Oxford Pain Relief Unit, Churchill Hospital.

  • Oxford Respiratory Group

    15 January 2013

    NDA

    The Oxford Respiratory Group works collaboratively on a range of projects dedicated to Respiratory Control. Professor Pandit's group studies anaesthetic effects on oxygen sensing and also focusses on clinical research related to effects of anaesthetics on respiration and anaesthetic techniques on the lungs and airway.

  • Oxford Airway Group

    15 January 2013

    NDA

    We strive to continually improve airway management in anaesthesia with a focus on minimising risk associated with difficult airways.

  • Circadian and Visual Neuroscience (Foster)

    15 January 2013

    NLO

    Our research interests range across the neurosciences but with specific interests in circadian, visual and behavioural neuroscience.

  • Circadian and Visual Neuroscience (Peirson)

    15 January 2013

    NLO

    Our research focuses on the non-image forming function of the eye, including how the light environment regulates sleep and circadian rhythms and how these responses are affected in disease.