The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis

Nakayama, Kohzo; Ohkawara, Takeshi; Hiratochi, Masahiro; Koh, Chang−Sung; Nagase, Hisashi

doi:10.1016/j.neulet.2008.08.034

Cited by 41 publications

(50 citation statements)

References 30 publications

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“…Several researchers have suggested that AICD plays an active role in triggering the apoptotic response (39,44,65,67). Recently, we found that various lengths CTs, including AICD and CT31, can translocate to the nucleus and exert apoptosis, and mutant studies have suggested that the YENPTY domain is most important for inducing neurotoxicity (unpublished data).…”

Section: Putative Role Of Aicd As a Modulator Of Apoptosismentioning

confidence: 82%

Possible roles of amyloid intracellular domain of amyloid precursor protein

Chang¹,

Suh²

2010

BMB Reports

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Section: Putative Role Of Aicd As a Modulator Of Apoptosismentioning

confidence: 82%

Possible roles of amyloid intracellular domain of amyloid precursor protein

Chang¹,

Suh²

2010

BMB Reports

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“…As mentioned above, the highest degree of sequence conservation within the APP homologues is found in the ICD [9,29]. This sequence conservation suggests the functional importance of AICD, which may reflect the existence of APP signaling.…”

Section: Signaling Functions Of Aicdmentioning

confidence: 98%

“…Interestingly, the amino acid sequence of the Aβ fragment is not highly conserved and is unique to APP; on the other hand, the highest degree of sequence conservation is found in the ICD not only within the APP homologues [29] but also within the APP family [9]. This strong sequence conservation most likely reflects functional importance of the ICDs in the APP family proteins.…”

Section: Overview Of Appmentioning

confidence: 99%

“…To explore APP signaling, we established several AICD-overexpressing embryonic carcinoma P19 cell lines [29]. Undifferentiated AICD-overexpressing cells retained epithelial cell-like morphology and healthy as well as control cells.…”

Section: Signaling Functions Of Aicdmentioning

confidence: 99%

“…To test the hypothesis that APP has a signaling mechanism similar to that of Notch, we established embryonic carcinoma P19 cell lines that overexpressed AICD [29], which may mimic signaling mechanisms. Although neurons differentiated from these cell lines, AICD expression induced dynamic changes in gene expression profile and neuron-specific apoptosis [30].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

γ-Secretase — Regulated Signaling and Alzheimer's Disease

Nakayama¹,

Nagase²,

Koh³

et al. 2013

Understanding Alzheimer's Disease

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c‐Abl modulates AICD dependent cellular responses: Transcriptional induction and apoptosis

Vázquez

Vargas

Inestrosa

et al. 2009

Journal Cellular Physiology

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APP intracellular domain (AICD) has been proposed as a transcriptional inductor that moves to the nucleus with the adaptor protein Fe65 and regulates transcription. The two proteins, APP and Fe65, can be phosphorylated by c-Abl kinase. Neprilysin has been proposed as a target gene for AICD. We found that AICD expression is decreased by treatment with STI-571, a c-Abl inhibitor, suggesting a modulation of AICD transcription by c-Abl kinase. We observed interaction between c-Abl kinase, the AICD fragment and the Fe65 adaptor protein. In addition, STI-571 reduces apoptosis in APPSw, and the apoptotic response induced by Fe65 over-expression was inhibited by with the expression of a kinase dead (KD) c-Abl and enhanced by over-expression of WT-c-Abl. However, in the APPSw cells, the ability of the KD-c-Abl to protect against Fe65 was reduced. Finally, in APPSw clone, we detected higher trans-activation of the pro-apoptotic p73 isoform, TAp73 promoter. Our results show that c-Abl modulates AICD dependent cellular responses, transcriptional induction as well as the apoptotic response, which could participate in the onset and progression of the neurodegenerative pathology, observed in Alzheimer's disease (AD).

show abstract

The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis

Cited by 41 publications

References 30 publications

Possible roles of amyloid intracellular domain of amyloid precursor protein

Possible roles of amyloid intracellular domain of amyloid precursor protein

γ-Secretase — Regulated Signaling and Alzheimer's Disease

c‐Abl modulates AICD dependent cellular responses: Transcriptional induction and apoptosis

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