Cell Biology

Losing Control

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Science  17 Oct 2008:
Vol. 322, Issue 5900, pp. 348
DOI: 10.1126/science.322.5900.348c

Parkinson's disease is a neurodegenerative disorder that affects 1% of people over 65, rising to 5% of those over 85. Nerve cells in the brain produce the neurotransmitter dopamine, which controls the smooth movement of muscle. In Parkinson's patients, these dopaminergic neurons are damaged, causing them to fire inappropriately and affect controlled body movements. The most common molecular cause of Parkinson's disease is a mutation in the gene encoding leucine-rich repeat kinase 2 (LRKK2); however, how this causes neuronal degeneration has been unclear. Now Imai et al. find that LRRK2 regulates the production of proteins in the cell during a stress response. When environmental conditions change, a cell needs to rapidly respond in order to survive. One effective way of doing this is by quickly generating additional proteins by translating existing mRNA. Both human and Drosophila forms of LRRK2 phosphorylated the translational regulator, eukaryotic initiation factor 4E-binding protein. This caused an increase in protein translation and attenuated resistance to oxidative stress and survival of dopaminergic neurons. In some patients, mutant LRRK2 has increased kinase activity, which could cause cells to lose control of translation. Thus, deregulated protein translation could affect the neurodegeneration seen in Parkinson's disease. — HP*

EMBO J. 27, 2432 (2008).

  • *Helen Pickersgill and Chris Surridge are locum editors in Science's editorial department.

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