By E. Grote, F. Bonzelius, G. Herman (auth.), K. S. Kosik M.D., D. J. Selkoe M.D., Y. Christen Ph.D. (eds.)
Like the unflinching gaze of Captain Ahab jogging the deck of the Pequod, Alzheimer researchers have had their attractions fastened firmly at the sickness for a few years. Now, as this quantity amply demonstrates, finished researchers from different fields, who've notion deeply approximately telephone organic difficulties are making use of their insights to Alzheimer's ailment. The contri butions right here signify the textual content types of the complaints from the 10th "Colloque medecine et recherche" of the Fondation IPSEN dedicated to learn on Alzheimer's sickness. The symposium, entitled "Alzheimer's disorder: classes from telephone Biology" was once held in Paris on April 25, 1994. As is clear from the numerous backgrounds of the individuals, the clinical pursuit of Alzheimer's disorder has started to meld with extra simple disciplines, really cellphone biology. whereas at the one hand, new components of specialization are continually rising, the limits of older disciplines are increas ingly blurred. possibly for many of the years because the first descriptions of the illness in 1907, the technological know-how of Alzheimer's disorder was once descriptive, and lay within the province of pathologists. this period of time, in which very much used to be realized in regards to the topography of senile plaques and neurofibrillary tangles, culminated with an ultrastructural description of those hallmark buildings. the trendy period of Alzheimer's disorder study opened with the iden tification of the part proteins in plaques and tangles.
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Additional info for Alzheimer’s Disease: Lessons from Cell Biology
Cell 75: 1039-1042 Lian JP, Ferro-Novick S (1993) Bos1p, an integral membrane protein of the endoplasmic reticulum to golgi transport vesicles, is required for their fusion competence. Cell 73: 735-745 Lombardi D, Soldati T, Riederer MA, Goda Y, Zerial M, Pfeffer SR (1993) Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J 12: 677-682 Novick P, Brennwald B (1993) Friends and Family. The role of the Rab GTPases in vesicular traffic. Cell 75: 597-601 NUOffer C, Davidson HW, Matteson J, Meinkoth J, Balch WE (1994) A GDP-bound form of Rab1 inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments.
Again, these results strongly suggest that the y-secretase must act after sorting occurs and also must be found in both the apical and basolateral domains. Whether the y-secretase is found on the plasma membrane, in post-Golgi vesicles, or in endosomes remains an important unknown. Mechanisms of Molecular Sorting in Polarized Cells: Relevance to Alzheimer's Disease 25 These results are interesting in several respects. First, although still somewhat preliminary, they put some constraints on the intracellular sites at which the various secretase enzymes are likely to be found: p-secretase in the cisternal Golgi, a- and y-secretase in post-Golgi compartments that occur at both cytoplasmic/plasma membrane domains of MDCK cells.
The Alzheimer's amyloid precursor protein (APP) is expressed by polarized cell types such as endothelial and neuronal cells. Thus, we analyzed its intracellular transport in the MDCK kidney epithelial cell line and asked whether mutations in the APP gene that lead to familial early onset Alzheimer's disease have any effect on the polarity of APP transport or the release of amyloidogenic fragments. Wild type APP is transported to the basolateral surface due to a basolateral targeting signal in its cytoplasmic domain.