The findings are reported by Vik Khurana, Mel Feany, and colleagues from Brigham and Women's Hospital, Harvard Medical School, and the Burnham Institute.
Neurons in the brain generally do not divide. It is therefore perplexing that in Alzheimer's disease, and other dementias associated with a protein called tau, dying neurons actually re-express proteins normally seen during cell division or in cancer. It has previously been unclear whether such cell-division proteins cause neuronal death, protect neurons from death, or are irrelevant.
In the present work, the researchers used a fruit-fly model of Alzheimer's disease to examine the relationship of cell-division proteins to neurodegeneration. The power of this model, which recapitulates key features of the human disease, lies in the ability to use genetic tools to establish a causal connection between a molecular pathway and neuronal death. Khurana and colleagues found that, as in human disease, abnormal expression of cell-cycle proteins accompanied neuronal death in their fly model. Most importantly, loss of neurons could be prevented when the cell cycle was genetically blocked or when flies were fed anticancer drugs. Cell-cycle activation depended upon a hyperactive cell growth molecule, TOR (target of rapamycin), also known to be abnormally activated in Alzheimer's disease. By establishing these causal connections, this study suggests that anticancer drugs are potential therapies for Alzheimer's disease and related disorders. More broadly, the results point to an intriguing connection between cancer and dementia, two of the most important diseases in the elderly.
The researchers include Vikram Khurana, Yiran Lu, Michelle L. Steinhilb, Joshua M. Shulman, and Mel B. Feany of the Brigham and Women's Hospital and Harvard Medical School in Boston, MA; Sean Oldham of The Burnham Institute in La Jolla, CA. This work was supported by Fulbright, H.C.N.R., and American Australian Association/Merck Foundation Fellowships to V.K., and by NIH (AG88001, AG19790) and McKnight Foundation grants to M.B.F.
Khurana et al.: "TOR-Mediated Cell-Cycle Activation Causes Neurodegeneration in a Drosophila Tauopathy Model." Publishing in Current Biology 16, 230–241, February 7, 2006. DOI 10.1016/j.cub.2005.12.042. www.current-biology.com
Journal
Current Biology