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Trends Mol Med. 2004 Oct;10(10):476-80.

Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection.

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Department of Molecular Biology, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.


DENN/MADD is a component of a signalling protein complex that is localized to the cytosol and exerts multiple functions by using different binding partners. Human DENN/MADD is physically the same death-domain protein as rat Rab3 GDP/GTP exchange protein (Rab3GEP). DENN/MADD regulates the recycling of Rab3 small G proteins under normal conditions and has an essential role in Ca(2+)-dependent neurotransmitter release and exocytosis. It is also involved in blocking the apoptosis of neuronal cells under conditions of cytotoxic stress. Recent research supports an important role for DENN/MADD in neuroprotection: reduced endogenous DENN/MADD expression and enhanced pro-apoptotic signalling has been found in brains affected by Alzheimer's disease.

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