Motor neuron control of skeletal muscle is affected in a wide range of inherited and acquired neuromuscular diseases with severe impact on mobility and life expectancy. In amyotrophic lateral sclerosis (ALS), for example, the rapid deterioration of motor neurons leads on average to death in 3-5 years due to respiratory failure. There is also a growing awareness that peripheral nervous system dysfunction, including motor neuron loss, during aging could contribute to mobility disability in frailty and sarcopenia. With declining mobility in the elderly associated with a high incidence of other debilitating diseases such as diabetes, cardiovascular problems and even declining cognitive function, it is clear that maintaining motor control will be key to sustaining a healthy aging population. Within the peripheral nerve group of the Musculoskeletal Disease Area (MSD) we have focused our research efforts around iPS-technology and patient-derived cells in collaboration with colleagues from the Chemical Biology & Therapeutics department. Using genetically-defined diseases as a starting point, we are establishing in vitro model systems of motor neuron and neuromuscular pathophysiology that we hope could ultimately have application for age-related dysfunction.
BCTP, a classic polymodal inhibitor of TRPV1 with a reduced liability for hyperthermia, is analgesic and ameliorates visceral hypersensitivity.
Nash MS, McIntyre P, Groarke A, Lilley E, Culshaw A, Hallett A, Panesar M, Fox A, Bevan S.
J Pharmacol Exp Ther. 2012 Aug;342(2):389-98.
Glial cell-derived neurotrophic factor enhances synaptic communication and 5-hydroxytryptamine 3a receptor expression in enteric neurons.
Zeng F, Watson RP, Nash MS.
Gastroenterology. 2010 Apr;138(4):1491-501.
Synaptic activity augments muscarinic acetylcholine receptor-stimulated inositol 1,4,5-trisphosphate production to facilitate Ca2+ release in hippocampal neurons.
Nash MS, Willets JM, Billups B, John Challiss RA, Nahorski SR.
J Biol Chem. 2004 Nov 19;279(47):49036-44.
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