Structural and functional insights into the biological function of mouse proNGF

In the recent years one of the lines of in vestigation in the Neur obiology Laboratory at SISSA has been to study the molecular det erminants of Alzheimer’s Disease (AD), one of the most known and diffused neur odegenerative aging diseases. AD is characterized by lesions in the brai n cortex, including the presence of β -amyloid plaques and neurofibrillary tangles c ontaining phosphorylated tau protein. In Alzheimer’s disease neuronal degeneration is found in selected areas of the brain, in particular in cortical, hippocam pal and basal forebrain cholinergic neurons (reviewed in Price et al ., Ann. Rev. Neurosci., 1986) . The investigation on the involvement of the neurotrophin Nerve Gr owth Factor (NGF) in AD has been extensive, because it promotes the survival and regulates the function of cholinergic neurons of the basal forebr ain. (reviewed in Counts et al. , J. Neuropath. Exp. Neuro., 2005). NGF is translated as a pre- pro-protein, proNGF, the im portance of which in the recent years has grown much, thanks to impor tant findings on its bi ological functions, besides the one of promoting protein foldin g. Accordingly, the increasing number of involved new actors has complicated also t he scenario of the investigations on the molecular determinants in AD.