Researchers studying the connections between neurons in fruit flies may have identified mechanisms which are involved neurodegeneration in Frontotemporal Dementia (FTD). FTD affects the frontal and temporal lobes (in human brains). A protein called CHMP2B can cause neuronal connections to grow incorrectly in fruit flies. The research has identified mechanisms which appear to control how CHMP2B functions; so potentially yielding insights into possible drug targets for the development of therapies for FTD in future.
Earlier research by the same team created a fruit fly model of frontotemporal dementia, involving flies with a defective form of CHMP2B. This model was used to identify other proteins which interact with CHMP2B and which may influence the development of frontotemporal dementia. Another protein called RAB8 was identified.
In this latest research, the researchers used fruit flies, which lack the RAB8 protein, to explore the role of RAB8 deficiency on basic mechanisms which result in a characteristic overgrowth of the connections between neurones and muscles. Neuromuscular junctions were overgrown in a RAB8 mutant fly. It is thought that RAB8 may be involved in regulating the growth of neurones which are affected in FTD; and that RAB8 may slow this type of neurodegeneration.
The same researchers have identified other proteins (POSH, and TAK1) which may prevent or slow the degeneration of neurones involved in FTD, again using their fruit fly models.
Note: This is early stage research, and further research would be required to confirm whether similar mechanisms are actually at work in human FTD disease progression.
Research identifies new steps in dementia progression. London: Alzheimer’s Society, March 30th 2015.
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West, RJ. Lu, Y. [and] Marie, B. [et al] (2015). Rab8, POSH, and TAK1 regulate synaptic growth in a Drosophila model of frontotemporal dementia. The Journal of Cell Biology. March 23rd 2015, 208(7), pp. 931-947. (Click here to view the PubMed abstract).
There is related JCB editorial comment:
Short, B. (2015). A POSH accent for synaptic growth. The Journal of Cell Biology. March 23rd 2015, 208(7), p.860.