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Linda Greensmith

Linda Greensmith

The work in our laboratory is aimed at improving our understanding of the mechanisms involved in motoneuron degeneration, with particular reference to the loss of motoneurons that occurs in motor neuron diseases such as Amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder in which motoneurons in the spinal cord and brain progressively die, resulting in muscle paralysis and death, typically within 2-5 years of diagnosis.

Primary Astroglia

There is currently no cure or effective treatment for this disease. It is therefore essential that we increase our understanding of the pathophysiology of this disease in order to help us to develop an effective therapy.

We are also beginning to investigate the pathogenesis of other motoneuron disorders. In collaboration with Drs Mary Reilly and Henry Houlden of the MRC Centre, we have recently started to motoneuron degeneration in forms of Charcot-Marie-Tooth Disease (CMT), the most common hereditary disorder of the peripheral nervous system. Distal hereditary motor neuropathy (dHMN), the spinal form of CMT, is an exclusively motor disorder of the PNS.

Skeletal muscle endplates and motor neuron

Recently, a number of mutations in a small heat shock protein, Hsp27, have been identified in patients by Drs Reilly and Houlden that are linked to dHMN. Hsp27 belongs to a family of stress-response proteins that are important for neuronal function and survival. We are studying the cellular mechanism by which mutations in Hsp27 result in axonal degeneration and motoneuron death in dHMN.
Skeletal muscle endplates and motor neuron

Several pathological mechanisms play a role in the death of motoneurons in these disorders. In our group we have been investigating some of these mechanisms, for example the role of i) protein chaperones, ii) axonal transport defects (in Collaboration with Dr Giampietro Schiavo, CRUK), iii) mitochondrial deficits (in collaboration with Prof Michael Duchen of the MRC Centre) and iv) axonal excitability defects (with Prof Hugh Bostock of the MRC Centre). We hope that a greater understanding of the causative factors involved in the death of motor neurons may help us to identify new therapeutic targets.

Primary Motorneurons

We use a multidisciplinary approach, examining a variety of animal models of motor dysfunction (in collaboration with Prof Elizabeth Fisher of the MRC Centre) as well primary cell cultures of motoneurons, muscles and glial cells. We also use a wide range of techniques from cellular and molecular biology to whole animal systems physiology. The overall aim of our research program is to help in the development of effective therapeutic strategies for use in the treatment of these debilitation and often fatal neurodegenerative disorders.

Professor Linda Greensmith PhD
Professor of Neuroscience
The Graham Watts Laboratories for Research into Motor Neuron Disease

Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology
Queen Square
London WC1E 6BT

Telephone: 020 7676 2161
Fax: 020 7813 1673
Email: l.greensmith@ucl.ac.uk

Links

http://www.ion.ucl.ac.uk/research/sobell/greensmith.htm

http://www.ucl.ac.uk/ion/departments/sobell/Research/LGreensmith