Snapshot Issue 38 September 2007


Scientists never lack inspiration when it comes to giving a new protein, a name. Some names, such as cupidin or titin, flirt with the realms of poetry – or perhaps the lack of it – while others implicitly suggest a protein’s function. Aquaporin, a pore designed for water, is an example. Other names suggest a physical trait or an illness a protein may be involved in. The name "dardarin" was given to one such protein. "Dardara" is a word used in the Basque Country and means "trembling", one of the familiar symptoms of Parkinson’s disease.

Parkinson’s is a neurological disorder, characterized by the loss of certain nerve cells which cause muscular stiffness, slow movements and trembling. Although the first symptoms usually appear after the age of 50, some rare hereditary forms can break out earlier and progress rapidly. Dardarin is associated with the PARK8 hereditary form of Parkinson’s disease – a very particular form since the first symptoms “only” appear after the age of 50. This particular form progresses slowly and hits every member of a family, generation upon generation.

"Dardarin" – also known as LRRK2 – was discovered following the study of a number of Basque families. When researchers compared data with other families world wide, they discovered some twenty mutations in the dardarin gene, each of which was linked to the PARK8 form of Parkinson’s disease. Twenty mutations is an awful lot for one hereditary disorder. Indeed, any one mutation which can be directly associated with a disease, is already a rare event.

Why such a fate? What does nature have against dardarin? Dardarin is a kinase, i.e. it adds phosphate onto other proteins. The effects the numerous mutations have on dardarin are not all known. However, whether its activity is increased or – on the contrary – decreased, mutations on the protein must somehow affect the state of phosphorylation of key proteins in Parkinson’s disease. Meanwhile, the normal activity of dardarin in brain cells remains a mystery.

PARK8 is a very rare form of Parkinson’s disease, and represents only 5 to 10% of all family cases of the illness. Despite the surprising fact that patients suffering from PARK8 are not subject to the well-known tremble – which gives little credit to the name "dardarin" in this case – dardarin offers new perspectives in the understanding of Parkinson’s disease for future diagnoses and forms of therapy.

Also read Protein Snapshots: "Titin", and "Cupidin" and "Aquaporin"

LRRK2, Homo sapiens (human): Q5S007

L'édition française de cette chronique est disponible dans l'Instantanés du mois de Prolune.

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