Antibody-Regulated Neurotoxic Function of Cell-Surface β-Amyloid Precursor Protein

Sudo, Haruka; Jiang, Hong; Yasukawa, Takashi; Hashimoto, Yuichi; Niikura, Takako; Kawasumi, Masaoki; Matsuda, Shuji; Takeuchi, Y.; Aiso, Sadakazu; Matsuoka, Masao; Murayama, Yoshitake; Nishimoto, Ikuo

doi:10.1006/mcne.2000.0910

Cited by 60 publications

(69 citation statements)

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“…As Rohn et al (2000) and Sudo et al (2000Sudo et al ( , 2001 reported independently, treatment of primary neurons with anti-APP antibody 22C11 resulted in significantly increased cell death (Fig. 2).…”

Section: Effect Of Shn and Its Derivatives On Neuronal Death By Anti-supporting

confidence: 68%

“…Stained cells were counted within 3 min after the mixture with trypan blue solution. The primary culture of mouse cortical neurons was performed in poly-D-lysine-coated 24-well plates (Sumitomo Bakelite, Akita, Japan), in the absence of serum and the presence of N2 supplement, as described previously (Sudo et al, 2000). The purity of neurons by this method was Ͼ98%.…”

Section: Methodsmentioning

confidence: 99%

“…FAD mutant PS1 enhances death in PC12 cells (Guo et al, 1996;Weihl et al, 1999) and primary neurons (Czech et al, 1998;Zhang et al, 1998;Guo et al, 1999;Weihl et al, 1999). Rohn et al (2000) and Sudo et al (2000Sudo et al ( , 2001 independently found that treatment of neuronal cells with anti-APP antibody remarkably enhances the neurotoxic function of wild-type (wt) APP, whose overexpression could cause AD type of neurodegeneration in Down's syndrome. Therefore, an important clue in the development of AD therapy would be provided by finding the molecules that suppress neuronal cell death by these AD-relevant insults.…”

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confidence: 99%

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Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

et al. 2001

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A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants of amyloid precursor protein (APP), M146L-presenilin (PS) 1, and N141I-PS2] and by A␤1-43 with clear action specificity ineffective on neurotoxicity by polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit neurotoxicity by other AD-relevant insults: other familial AD genes (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, and H163R-PS1), APP stimulation by anti-APP antibody, and other A␤ peptides (A␤1-42 and A␤25-35). The action specificity was further indicated by the finding that HN could not suppress neurotoxicity by glutamate or prion fragment. Against the AD-relevant insults, essential roles of Cys 8 and Ser 14 were commonly indicated, and the domain from Pro 3 to Pro 19 was responsible for the rescue action of HN, in which seven residues turned out to be essential. We also compared the neuroprotective action of S14G HN (HNG) with that of activity-dependent neurotrophic factor, IGF-I, or basic FGF for the antagonism against various AD-relevant insults (V642I-APP, NL-APP, M146L-PS1, N141I-PS2, and A␤1-43). Although all of these factors could abolish neurotoxicity by A␤1-43, only HNG could abolish cytotoxicities by all of them. HN and HN derivative peptides may provide a new insight into the study of AD pathophysiology and allow new avenues for the development of therapeutic interventions for various forms of AD.

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Section: Effect Of Shn and Its Derivatives On Neuronal Death By Anti-supporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

et al. 2001

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“…Transfection efficiency was consistently 60-70%, as described (12). The primary culture of mouse cortical neurons was performed as described (15). Prepared neurons (1.25 ϫ 10 5 cells/ well) were preincubated with or without 10 nM or 10 M sHN for 16 h, and treated with 25 M A␤1-43 in the presence or absence of 10 nM or 10 M sHN for 24-72 h. To prevent transient dryness, we changed half volume of medium with prewarmed fresh medium containing 50 M A␤1-43 and 10 nM or 10 M sHN.…”

Section: Methodsmentioning

confidence: 99%

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

Hashimoto

Niikura

Tajima

et al. 2001

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

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There is no proof that the HN cDNA represents a gene, that its origin is nuclear, or that the HN peptide is produced in vivo. The information that the long HN cDNA sequence is virtually identical to mitochondrial rRNA should have been put in the Discussion rather than published as supplementary material. The Discussion should have contained the following:The long cDNA [1,567 bp including a poly(A) tail] containing the HN ORF is Ͼ99% identical (1548͞1552) to positions 1679-3230 of mitochondrial DNA (GenBank accession no. AB055387). Because mitochondrial DNA positions 1667-3224 code for mitochondrial 16S rRNA, and mitochondrial 16S rRNA has a short poly(A) tail during transcription (1), the virtual identity of the long HN cDNA to mitochondrial DNA indicates that HN cDNA is mitochondrial 16S rRNA with a poly(A) tail. This makes it unlikely that the peptide encoded by the ORF in HN cDNA is naturally produced. Further, the 75-bp HN ORF is separated from the 5Ј end of the long HN cDNA by a 950-bp region containing at least seven ORFs, each with a stop codon. This makes it even more unlikely that HN peptide is produced from the long HN cDNA. It should also be noted that mitochondria-like nuclear sequences occur commonly as pseudogenes (2). Finally, the HN peptide lacks the characteristic N-terminal signal sequence of secreted peptides, although we suggest that a signal peptide-like function may be encoded in the primary sequence of HN peptide. For all of these reasons, it is unlikely that the HN ORF leads to production of the predicted peptide in vivo.Nonetheless, it remains possible that HN cDNA represents a nuclear transcribed mRNA and that the HN peptide is a natural product. Long regions of the HN cDNA are Ͼ99% identical to certain registered human mRNAs [1545͞1553 at positions 14-1580 of FLJ22981 fis cDNA (AK026634), 925͞929 at positions 1-929 of FLJ22517 fis cDNA, 914͞919 at positions 1348-2266 of FLJ20341 fis cDNA, and 345͞346 at positions 1-346 of PNAS-32 mRNA]. PNAS-32 mRNA is actually expressed to produce NB4 apoptosis-related protein, showing that this mRNA is transcribed from a nuclear gene. In addition, HN cDNA is highly similar to regions of more than 1,000 bp on human chromosomes [positions 245364-244075 of chromosome 11 draft sequence (92%, 1198͞1290), positions 65752-66775 of chromosome X draft sequence (95%, 974͞1025), and positions 687598-688608 of chromosome 5 draft sequence (93%, 954͞1016)]. Also, the HN ORF has a Kozak-like sequence, although it is not canonical.

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“…F11 cells are the hybrid of a rat embryonic day 13 primary cultured neuron with a mouse neuroblastoma NTG18 and have so far been used as the best model for primary neurons (Yamatsuji et al 1996;Storms and Rutishauser 1998;Ghil et al 2000;Hagiwara et al 2000;Hashimoto et al 2000aHashimoto et al ,b, 2001aHashimoto et al ,b,c, 2003aHashimoto et al , 2004aHuang et al 2000;Sudo et al 2000Sudo et al , 2001Niikura et al 2001). F11 cells overexpressing L401K p75NTR (F11/L401K cell) were established as follows.…”

Section: Genes and Chemical Materialsmentioning

confidence: 99%

Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid‐β peptides via p75NTR/PLAIDD

Hashimoto¹,

Kaneko²,

Tsukamoto³

et al. 2004

Journal of Neurochemistry

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One of the most important pathological features of Alzheimer's disease (AD) is extracellular senile plaques, whose major component is amyloid-b peptides (Ab). Ab binds to the extracellular domain of p75NTR (p75 neurotrophin receptor) and induces neuronal cell death. We investigated the molecular mechanism of Ab-induced neurotoxicity in detail from the standpoint of interaction between p75NTR and its recently identified relative, PLAIDD (p75-like apoptosis-inducing death domain). Using F11 neuronal hybrid cells, we demonstrate that there are two distinct pathways for Abinduced toxicity mediated by p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR, Go, JNK, NADPH oxidase and caspase3-related caspases. We found that PLAIDD and Gi proteins, heterotrimeric G proteins, are involved in the alternative Ab-induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by Ab is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3-related caspases. In addition, we found that HN, ADNF, IGF-I, or bFGF inhibits both pathways of Ab-induced neurotoxicity mediated by p75NTR. Amyloid-b peptides (Ab) are the major constituent of the senile plaques in Alzheimer's disease (AD). Ab, the 39-43 amino acids peptide, is produced by the b-and c-secretasemediated cleavage of amyloid precursor protein (APP). Formation and accumulation of Ab have been inferred to contribute to the development of AD. In vitro, increased levels of Ab concentration cause cell death in primary cultured neurons as well as some neuronal line cells (Yankner et al. 1989;Loo et al. 1993;Gschwind and Huber 1995;Kaneko et al. 1995;Pike et al. 1997;Giovanni et al. 1999;Sudo et al. 2001). However, the precise mechanism underlying Ab neurotoxicity remains to be elucidated.One possible mechanism for Ab-induced neurotoxicity is that Ab binds to its putative receptor on the neuronal cell membrane and triggers the intracellular death signal. Multiple proteins have been so far claimed to be candidates for the Ab receptor. They include the receptors for the endoplasmic reticulum Ab-binding dehydrogenase (ERAB;Yan et al. 1997a), the advanced glycation end products (Yan et al. 1997b), the a7 nicotinic acetylcholine receptor (Wang Address correspondence and reprint requests to M. Matsuoka, Department of Pharmacology, KEIO University School of Medicine, Shinanomachi, Tokyo, Japan. E-mail: sakimatu@sc.itc.keio.ac.jpAbbreviations used: Ab, amyloid beta; AD, Alzheimer's disease; ADNF, activity-dependent neurotrophic factor; APO, apocynin; APP, amyloid precursor protein; BBP-1, b-amyloid binding protein-1; bFGF, basic fibroblast growth factor; DPI, diphenyleneiodonium chloride; ERAB, endoplasmic reticulum Ab-binding dehydogenase; FBS, fetal bovine serum; GEE, gluthione-ethyl-ester; HN, Humanin; HRP, horseradish peroxidase; JNK, c-Jun N-terminal kinase; NFkB, nuclear factorkB; NOS, nitric oxide synthase; (p75-like apoptosis-inducing death domain) p75NTR, 75 kDa neurotrophin receptor; PTX, pertussis toxin; ROS, reactive ox...

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Antibody-Regulated Neurotoxic Function of Cell-Surface β-Amyloid Precursor Protein

Cited by 60 publications

References 58 publications

Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

Detailed Characterization of Neuroprotection by a Rescue Factor Humanin against Various Alzheimer's Disease-Relevant Insults

A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ

Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid‐β peptides via p75NTR/PLAIDD

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