Retinoic acid induced differentiated neuroblastoma cells show increased expression of the βA4 amyloid gene of Alzheimer's disease and an altered splicing pattern

König, Gerhard; Masters, Colin L.; Beyreuther, Konrad

doi:10.1016/0014-5793(90)81181-m

Cited by 104 publications

(52 citation statements)

References 36 publications

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“…4). When we used differentiated SH-SY5Y cells (induced by retinoic acid treatment [14]), we found no difference in the clearance rate from non-treated SH-SY5Y cells (data not shown).…”

Section: N Ida Et Alifebs Letters 394 (1996) 174-178mentioning

confidence: 87%

Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells

1996

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Cerebral deposition of [~A4 (~-amyloid) peptide is a major pathological feature of AIzheimer's disease. Although the mechanism of [~A4 production from cells has been investigated extensively, so far little is known about the catabolism of the peptide. We report here that the human neuroblastoma cell line SH-SY5Y can rapidly clear [~A4 in the culture medium. The clearance was not due to the degradation by extraceilularly released protease, but rather due to intracellular degradation after cellular uptake. This clearance activity was specific to SH-SY5Y cells among several cell types examined. Some of the [~A4-derived peptides lacking the N-terminal part of the molecule were not catabolized, suggesting a specific interaction between the cells and ~A4. Although most of the peptide was degraded after uptake, small amounts of peptide was accumulated in insoluble fractions of the cells and remained stable for several days. These observations suggest that this uptake-degradation activity may contribute to AD pathogenesis in two different ways: either to prevent the amyloid deposition by reducing extracellular [~A4 concentrations, or to promote the deposition by producing insoluble seeds for amyloid formation.

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“…4). When we used differentiated SH-SY5Y cells (induced by retinoic acid treatment [14]), we found no difference in the clearance rate from non-treated SH-SY5Y cells (data not shown).…”

Section: N Ida Et Alifebs Letters 394 (1996) 174-178mentioning

confidence: 87%

Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells

1996

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“…For example, their level of gene expression is regulated during development of the nervous system (Lorent et al, 1995). Also, induction of neuronal differentiation in cultured cells increases expression of all three family members (Konig et al, 1990;Hung et al, 1992;Beckman and Iverfeldt, 1997). Furthermore, both APP and APLP2 are present in elongating axons (Moya et al, 1994;Thinakaran et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Disabled-1 Binds to the Cytoplasmic Domain of Amyloid Precursor-Like Protein 1

et al. 1999

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Disruption of the disabled-1 gene (Dab1) results in aberrant migration of neurons during development and disorganization of laminar structures throughout the brain. Dab1 is thought to function as an adapter molecule in signal transduction processes. It contains a protein-interaction (PI) domain similar to the phosphotyrosine-binding domain of the Shc oncoprotein, it is phosphorylated by the Src protein tyrosine kinase, and it binds to SH2 domains in a phosphotyrosine-dependent manner. To investigate the function of Dab1, we searched for binding proteins using the yeast two-hybrid system. We found that the PI domain of Dab1 interacts with the amyloid precursor-like protein 1 (APLP1). The association of Dab1 with APLP1 was confirmed in biochemical assays, and the site of interaction was localized to a cytoplasmic region of APLP1 containing the amino acid sequence motif Asn-Pro-x-Tyr (NPxY). NPxY motifs are involved in clathrin-mediated endocytosis, and they have been shown to bind to PI domains present in several proteins. This region of APLP1 is conserved among all members of the amyloid precursor family of proteins. Indeed, we found that Dab1 also interacts with amyloid precursor protein (APP) and APLP2 in biochemical association experiments. In transiently transfected cells, Dab1 and APLP1 colocalized in membrane ruffles and vesicular structures. Cotransfection assays in cultured cells indicated that APP family members increased serine phosphorylation of Dab1. Dab1 and APLP1 are expressed in similar cell populations in developing and adult brain tissue. These results suggest that Dab1 may function, at least in part, through association with APLP1 in the brain. Key words: reeler; scrambler; neuronal migration; phosphorylation; APLP1; signal transductionThe mutant mouse strains reeler (Falconer, 1951), scrambler (Sweet et al., 1996), and yotari and the mouse strain created by targeted disruption of the disabled-1 (Dab1) gene (Howell et al., 1997a,b) exhibit motor defects and ataxia associated with severe hypoplasia of the cerebellum (for review, see D' Arcangelo and Curran, 1998;Goldowitz and Hamre, 1998). In these mice, neuronal migration is disrupted throughout the brain, resulting in disorganization of many laminar structures, including the hippocampus, cerebral cortex, and cerebellum. Similar, but not identical, defects have been reported in two mutant mouse strains created by targeted disruption of the genes for cyclin-dependent kinase 5 (C dk5) and its neuronalspecific activator p35 (Ohshima et al., 1996;Chae et al., 1997). Characterization of the genes responsible for these mutations has provided a collection of molecules that participate in the signaling cascades responsible for choreographing neuronal migration in the developing brain. The task now facing the field is to understand how these proteins f unction and to elucidate their biochemical and biological relationships.The gene disrupted in reeler mice, reelin (D'Arcangelo et al., 1995), encodes a large extracellular protein that is secreted by pio...

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“…Many of the genes involved in these processes are retinoid target genes. RA receptors plus ligand regulate the expression of genes in a variety of cell types in the brain including, among others, MAPT (73,74), APP (74)(75)(76)(77)(78), PS2 (79), and beta-site APP-cleaving enzyme (80). IDE degrades amyloid plaque and is present in brain (21,81).…”

Section: Functions In Ad Of Retinoid-related Genesmentioning

confidence: 99%

“…IDE transcription is regulated by RA; the gene contains a RARA response element in its promoter (82). APP as precursor contributes to AB synthesis, but is not itself neurotoxic and promotes neurite outgrowth (75,78). RA has been shown to regulate the MAPT promoter (73).…”

Section: Functions In Ad Of Retinoid-related Genesmentioning

confidence: 99%

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Goodman¹,

Pardee²

2003

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

165

124

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The hypothesis of this article is that late onset Alzheimer's disease (AD) is influenced by the availability in brain of retinoic acid (RA), the final product of the vitamin A (retinoid) metabolic cascade. Genetic, metabolic, and environmental͞dietary evidence is cited supporting this hypothesis. Significant genetic linkages to AD are demonstrated for markers close to four of the six RA receptors, RA receptor G at 12q13, retinoid X receptor B at 6p21.3, retinoid X receptor G at 1q21, and RA receptor A at 17q21. Three of the four retinol-binding proteins at 3q23 and 10q23 and the RA-degrading cytochrome P450 enzymes at 10q23 and 2p13 map to AD linkages. Synthesis of the evidence supports retinoid hypofunction and impaired transport as contributing factors. These findings suggest testable experiments to determine whether increasing the availability of retinoid in brain, possibly through pharmacologic targeting of the RA receptors and the cytochrome P450 RAinactivating enzymes, can prevent or decrease amyloid plaque formation.

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Retinoic acid induced differentiated neuroblastoma cells show increased expression of the βA4 amyloid gene of Alzheimer's disease and an altered splicing pattern

Cited by 104 publications

References 36 publications

Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells

Rapid cellular uptake of Alzheimer amyloid βA4 peptide by cultured human neuroblastoma cells

Disabled-1 Binds to the Cytoplasmic Domain of Amyloid Precursor-Like Protein 1

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

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