Neurons are high maintenance, requiring a continuous supply of nurturing molecules. A shortage of one of these molecules might underlie one of the most common causes of dementia, Van Damme et al. report.
Unlike Alzheimer's disease, frontotemporal lobe dementia (FTLD) usually strikes people who are under the age of 65. Their fatal illness devastates the brain's frontal lobe, causing symptoms such as apathy and personality changes, or the temporal lobe, resulting in impaired speech or comprehension. Two years ago, researchers showed that some FTLD patients carry mutations in the gene for progranulin, a secreted protein that takes part in everything from tumor growth to inflammation. These glitches often reduce mRNA levels, suggesting that the disease stems from insufficient progranulin. But researchers knew little about progranulin's effects on the nervous system or how reduced levels could promote brain deterioration.
Van Damme et al. first determined whether progranulin levels are lower in FTLD. Samples of cerebrospinal fluid from patients contained much less progranulin than did samples from controls. To gauge the impact of this reduction, the team cultured rat neurons from the brain and spinal cord. Progranulin boosted their survival by up to 39%. After secretion, progranulin often gets snipped into multiple pieces, each of which might have a separate function. The researchers determined that one of these segments exerted the same cell-saving effect as full-sized progranulin. The findings point to progranulin as a potential treatment for FTLD.