Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro.

Allinquant, Bernadette; Hantraye, Philippe; Mailleux, Pierre; Moya, Kenneth L.; Bouillot, Colette; Prochiantz, Alain

doi:10.1083/jcb.128.5.919

Cited by 228 publications

(149 citation statements)

References 49 publications

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“…There is also evidence that A␤ (or APP) facilitates neurite outgrowth and synapse formation (56)(57)(58)(59). Although only culture experiments but not in vivo models (60) support this possibility to date, it is interesting to note that APP-deficient or knockout mice have a corpus callosum deficit (61), as is seen in PDAPP mice overexpressing APP, and aged APP knockout mice have a 12% volume deficit in the dentate gyrus of the hippocampus (60).…”

Section: Discussionmentioning

confidence: 99%

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis

Redwine

Kosofsky

Jacobs

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

177

102

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High-resolution magnetic resonance microscopy (MRM) was used to determine regional brain volumetric changes in a mouse model of Alzheimer's disease. These transgenic (Tg) mice overexpress human mutant amyloid precursor protein (APP) V717F under control of platelet-derived growth factor promoter (PDAPP mice), and cortical and hippocampal ␤-amyloid (A␤) deposits accumulate in heterozygotes after 8 -10 mos. We used MRM to obtain 3D volumetric data on mouse brains imaged in their skulls to define genotype-and age-related changes. Hippocampal, cerebellar, and brain volumes and corpus callosum length were quantified in 40-, 100-, 365-, and 630-day-old mice. Measurements taken at age 100 days, before A␤ deposition, revealed a 12.3% reduction of hippocampus volume in Tg mice compared with WT controls. This reduction persisted without progression to age 21 mos. A significant 18% increase in hippocampal volume occurred between 40 and 630 days in WT mice, and no corresponding significant increase occurred in Tg mice. Cavalieri volume estimates of hippocampal subfields from 100-day-old Tg mice further localized a 28% volume deficit in the dentate gyrus. In addition, corpus callosum length was reduced by Ϸ25% in Tg mice at all ages analyzed. In summary, reduced hippocampal volume and corpus callosum length can be detected by MRM before A␤ deposition. We conclude that overexpression of APP and amyloid may initiate pathologic changes before the appearance of plaques, suggesting novel targets for the treatment of Alzheimer's disease and further reinforcing the need for early diagnosis and treatment.T he essential neuropathologic features of Alzheimer's disease (AD) include the progressive deposition of amyloid plaques and neurofibrillary tangles in neocortical and hippocampal structures and a parallel global decrease in cortical volume (1, 2). Extensive data from analysis of postmortem human brain and mouse models of AD associate the neuropathology of AD with alterations in the expression, distribution, and deposition of ␤ amyloid protein (A␤). In AD brains, A␤ levels are increased, and the protein can be found in fibrillar chains within compact plaques, aggregated in diffuse plaques, or as oligomers and monomers in regions outside of plaques (3-6). Some of the known human mutations associated with AD affect the processing or cleavage of amyloid precursor protein (APP) and can cause increased A␤ levels or increase the relative amount of the primary plaque component A␤ 1-42 compared with A␤ 1-40 (3, 5-10). Other human mutations have been identified within the coding region of A␤ 1-42 , which can increase A␤ neurotoxicity (11). Transgenic (Tg) mouse models have shown that high levels of A␤ can cause AD-like amyloid plaque pathology. Tg mice that overexpress APP have some but not all deficits observed in AD (12, 13). Other Tg mouse models that have mutations associated with AD resulting in up-regulation of A␤ production have many, but not all, of the observed deficits seen in AD, including reduced hippocampal volume, reduced synap...

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Section: Discussionmentioning

confidence: 99%

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis

Redwine

Kosofsky

Jacobs

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

177

102

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“…This linkage catalyses an extremely efficient addressing of the oligonucleotide into the cell cytoplasm and nucleus (Allinquant et al, 1995). It allows the use of low concentrations of oligonucleotides, thus preventing undesirable effects of the polyanionic nature of oligonucleotides.…”

Section: Decreasing Sapp Reduces the Proliferation Of Egfresponsive Amentioning

confidence: 99%

Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone

et al. 2004

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“…These PTDs have no common feature, except the presence of basic amino acid residues (arginine and lysine), which may be involved in contact with the negatively charged lipids or in membrane penetration (9 -11). The PTDs also serve as trans-elements that facilitate membrane penetration by heterogeneous proteins and oligonucleotides (12)(13)(14)(15). Therefore, the major role of PTDs in these phenomena is presumed to be in the destabilization of the lipid bilayer.…”

mentioning

confidence: 99%

Protein Transduction Domain of HIV-1 Tat Protein Promotes Efficient Delivery of DNA into Mammalian Cells

Eguchi¹,

Akuta²,

Okuyama³

et al. 2001

Journal of Biological Chemistry

280

296

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The plasma membrane of mammalian cells is one of the tight barriers against gene transfer by synthetic delivery systems. Various agents have been used to facilitate gene transfer by destabilizing the endosomal membrane under acidic conditions, but their utility is limited, especially for gene transfer in vivo. In this article, we report that the protein transduction domain of human immunodeficiency virus type 1 Tat protein (Tat peptide) greatly facilitates gene transfer via membrane destabilization. We constructed recombinant phage particles displaying Tat peptide on their surfaces and carrying mammalian marker genes as part of their genomes (Tat-phage). We demonstrate that, when animal cells are briefly exposed to Tat-phage, significant expression of phage marker genes is induced with no harmful effects to the cells. In contrast, recombinant phage displaying other functional peptides, such as the integrin-binding domain or a nuclear localization signal, could not induce detectable marker gene expression. The expression of marker genes induced by Tatphage is not affected by endosomotropic agents but is partially impaired by inhibitors of caveolae formation. These data suggest that Tat peptide will become a useful component of synthetic delivery vehicles that promote gene transfer independently of the classical endocytic pathway.

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Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro.

Cited by 228 publications

References 49 publications

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis

Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis

Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone

Protein Transduction Domain of HIV-1 Tat Protein Promotes Efficient Delivery of DNA into Mammalian Cells

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