MOLECULAR MECHANISMS OF CHARCOT-MARIE-TOOTH DISEASE
Charcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system, affecting up to 1 in 1,200 people. The disease is characterised by degeneration of the peripheral nerves in the feet, legs, arms and hands, causing muscle weakness, loss of limb function, and mobility impairments. There is no cure for CMT, and patients frequently suffer lifelong disabilities.
We aim to model CMT in C. elegans in order to uncover novel information about how the disease develops, and provide a better understanding of the disease to offer valuable insight for the future generation of therapeutics. Our research focuses on axonal forms of CMT (classified as CMT2), and in particular on the most common axonal form, CMT2A, which is caused by mutations in Mitofusin 2, a protein critical for normal mitochondrial functioning.
DEFINING THE FUNCTION OF MITOFUSIN 2
In addition to modelling CMT2A, we are also investigating the function of the causative gene (Mfn2). Mfn2 is conserved in C. elegans, where it is know as fzo-1. We aim to uncover novel insights into the precise role of Mfn2/FZO-1 in mitochondrial dynamics and to identify novel regulators of its activity. Mfn2 is essential for normal mitochondrial health, and in addition to CMT2A is associated with other neurodegenerative (including Alzheimer's, Parkinson's, and Huntinton's diseases), and non-neuronal conditions, including metabolic (diabetes and obesity) and vascular proliferative diseases. As such, our studies aim to fully characterise the role of protein that it vital for normal cellular function and one that is linked to a variety of human disorders.