A cellular motor essential for nerve cell functions: impact on understanding of Huntington’s disease

September 06 2010

Huntington’s disease is characterised by atrophy in a specific area of the brain: the striatum. This atrophy may be related to dynein malfunction. Dynein is a protein that is vital for the transportation of molecules in neurons. These conclusions are drawn from research conducted by an international team of 23 researchers, coordinated by Luc Dupuis from Inserm unit 692 in Strasbourg and Albert Ludolph from the University of Uml (Germany). Their results are published on line in the Human Molecular Genetics review.

Huntington’s disease is a hereditary neurodegenerative disease affecting 6,000 people in France. It is caused by the mutation of a gene encoding protein synthesis: the Huntingtin gene. At an anatomic level, evidence of this is found in lesions in an integration centre in the brain: the striatum. Patients first display symptoms at around 45 and experience a progressive decline in their physical and mental aptitudes, until reaching dementia and eventually death. No treatments are currently available.

Motor and behavioural disorders in mutated mice

Since 2003, Inserm researchers in Strasbourg have been working on a stock of mutated mice with muscular problems and behavioural disorders (such as hyperactivity). Using MRI scans and cellular observations, the researchers have identified lesions in the stratiums of these mutated mice. “However, our mice do not have Huntington’s disease, since they do not have Huntingtin mutation and live entirely normally" clarifies Luc Dupuis.

Key role of dynein in neuron operations in the striatum

These mice display an encoding gene mutation for a molecular “motor”: dynein. Dynein is the only protein used to transport cargos (vesicular, protein-based, organelle) from the ends of axons and dendrites to the cell body. “We suspected that dynein was involved in the degeneration of stratial cells, but, thanks to this research, we now have direct proof of this link,” explains Luc Dupuis.

In this way, Huntington’s disease may be linked to dynein malfunction. This is an important hypothesis, since we know that dynein only moves at “full speed” if it is combined with other proteins, including Huntingtin. “Dynein carries many cargos. Our research now consists of establishing which transported cargos are essential for the stratium to function correctly. But this does not mean other leads to better understand Huntington's disease are to be neglected” underlines Luc Dupuis.

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Know more

A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons
Human Molecular Genetics

Contact chercheur
Luc Dupuis
Unité Inserm 692 ''Laboratoire de signalisations moléculaires et neurodégénérescence''
Faculté de médecine, Université de Strasbourg
Tél : 03 68 85 30 91

Luc Dupuis hails from Lille and has worked at the Inserm laboratory in Strasbourg, directed by Jean-Philippe Loeffler, for 13 years. Other than Huntington’s disease, his research also focuses on Charcot's disease, also known as lateral amyotrophic sclerosis.

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