UCL Institute of Neurology, in an international collaboration with colleagues in the United States, Paris and Tunisia, have published a paper confirming the role of the calcium-dependent protease calpain-1 in cerebellar ataxia.
The paper, “Defects in the CAPN1 gene result in alterations in cerebellar development and in cerebellar ataxia in mice and humans,” was published June 16, 2016 in Cell Reports.
Professor Henry Houlden, The National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology and Western U Graduate College of Biomedical Sciences Dean Professor Michel Baudry, are the Senior Co-authors.
Houlden, Baudry and collaborators identified genetic defects in ataxia families and studied the role of calpain-1 and calpain-2 in ataxia, synaptic plasticity, learning and memory and neurodegeneration. Another published paper shows a calpain-1 mutation in Parson Russell Terrier dogs is also associated with spinocerebellar ataxia. In the cerebellum, the knock-out mice had 10 percent less granule cells, which is not sufficient to account for ataxia. But they also had immature synapses, so the connection between the granule cells and Purkinje cells did not develop normally. The genetic mutations in calpain-1 in ataxia families result in abnormal development of the cerebellum, which is responsible for the ataxia. The team also demonstrated if they rescue this lack of calpain-1 during one postnatal week, they eliminated all the symptoms. The mice develop normally with no ataxia. They do not have loss of cells. This demonstrates that calpain-1 is neuroprotective. Mutation in calpain-1 are linked to excessive neurodegeneration and alterations in postnatal development.
For further details email: h.houlden@ucl.ac.uk