Carboxyl-terminal fragment of amyloid precursor protein and hydrogen peroxide induce neuronal cell death through different pathways

2006 ◽  
Vol 113 (12) ◽  
pp. 1837-1845 ◽  
Author(s):  
J. Sebastià ◽  
M. Pertusa ◽  
D. Vílchez ◽  
A. M. Planas ◽  
R. Verbeek ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Amyloid Precursor Protein ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Terminal Fragment ◽  
Carboxyl Terminal

Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death

2003 ◽  
Vol 84 (4) ◽  
pp. 864-877 ◽  
Author(s):  
Yuichi Hashimoto ◽  
Osahiko Tsuji ◽  
Takako Niikura ◽  
Yohichi Yamagishi ◽  
Miho Ishizaka ◽  
...  
Keyword(s):  
Cell Death ◽  
Amyloid Precursor Protein ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Precursor Protein

scholarly journals The Drosophila Amyloid Precursor Protein homologue mediates neuronal survival and neuro-glial interactions

2020 ◽  
Author(s):  
Irini A. Kessissoglou ◽  
Dominique Langui ◽  
Amr Hasan ◽  
Maral Maral ◽  
Suchetana Bias Dutta ◽  
...  
Keyword(s):  
Cell Death ◽  
Amyloid Precursor Protein ◽  
Transmembrane Protein ◽  
Neuronal Cell Death ◽  
Wnt Signaling Pathway ◽  
Physiological Role ◽  
Neuronal Cell ◽  
Adult Brain ◽  
Precursor Protein ◽  
Loss Of Function

AbstractThe amyloid precursor protein (APP) is a structurally and functionally conserved transmembrane protein whose physiological role in adult brain function and health is still unclear. Because mutations in APP cause familial Alzheimer’s disease, most research focuses on this aspect of APP biology. We investigated the physiological function of APP in the adult brain using the fruit fly Drosophila melanogaster, which harbors a single APP homologue called APP Like (APPL). Previous studies have provided evidence for the implication of APPL in neuronal wiring and axonal growth through the Wnt signaling pathway. However, like APP, APPL continues to be expressed in all neurons of the adult brain where its functions and their molecular and cellular underpinnings are unknown. We report that APPL loss of function results in the dysregulation of endolysosomal function, in both neurons and glia, with a notable enlargement of early endosomal compartment in neurons followed by neuronal cell death, the accumulation of dead neurons in the brain during a critical period at a young age and subsequent reduction in lifespan. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL is taken up by glia, regulates their endosomal morphology and this is necessary and sufficient for the clearance of neuronal debris in an axotomy model. We propose that the APP proteins represent a novel family of neuro-glial signaling proteins required for adult brain homeostasis.

Molecular Mechanisms for Neuronal Cell Death by Alzheimer’s Amyloid Precursor Protein-Relevant Insults

Neurosignals ◽  
2002 ◽  
Vol 11 (5) ◽  
pp. 236-250 ◽  
Author(s):  
Masaoki Kawasumi ◽  
Yuichi Hashimoto ◽  
Tomohiro Chiba ◽  
Kohsuke Kanekura ◽  
Yohichi Yamagishi ◽  
...  
Keyword(s):  
Cell Death ◽  
Amyloid Precursor Protein ◽  
Molecular Mechanisms ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Precursor Protein

scholarly journals The Drosophila amyloid precursor protein homologue mediates neuronal survival and neuroglial interactions

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000703 ◽  
Author(s):  
Irini A. Kessissoglou ◽  
Dominique Langui ◽  
Amr Hasan ◽  
Maral Maral ◽  
Suchetana B. Dutta ◽  
...  
Keyword(s):  
Cell Death ◽  
Amyloid Precursor Protein ◽  
Transmembrane Protein ◽  
Neuronal Cell Death ◽  
Wnt Signaling Pathway ◽  
Physiological Role ◽  
Neuronal Cell ◽  
Adult Brain ◽  
Precursor Protein ◽  
Loss Of Function

The amyloid precursor protein (APP) is a structurally and functionally conserved transmembrane protein whose physiological role in adult brain function and health is still unclear. Because mutations in APP cause familial Alzheimer’s disease (fAD), most research focuses on this aspect of APP biology. We investigated the physiological function of APP in the adult brain using the fruit fly Drosophila melanogaster, which harbors a single APP homologue called APP Like (APPL). Previous studies have provided evidence for the implication of APPL in neuronal wiring and axonal growth through the Wnt signaling pathway during development. However, like APP, APPL continues to be expressed in all neurons of the adult brain where its functions and their molecular and cellular underpinnings are unknown. We report that APPL loss of function (LOF) results in the dysregulation of endolysosomal function in neurons, with a notable enlargement of early endosomal compartments followed by neuronal cell death and the accumulation of dead neurons in the brain during a critical period at a young age. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL interacts with glia and regulates the size of their endosomes, the expression of the Draper engulfment receptor, and the clearance of neuronal debris in an axotomy model. We propose that APP proteins represent a novel family of neuroglial signaling factors required for adult brain homeostasis.

scholarly journals Low-DoseAronia melanocarpaConcentrate Attenuates Paraquat-Induced Neurotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
A. J. Case ◽  
D. Agraz ◽  
I. M. Ahmad ◽  
M. C. Zimmerman
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Reactive Oxygen ◽  
High Dose ◽  
Low Doses ◽  
Oxygen Species ◽  
High Doses

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson’s disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-richAronia melanocarpa(aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated neurotoxicity. Additionally, low doses of the concentrate attenuated the paraquat-induced increase in superoxide, hydrogen peroxide, and oxidized glutathione levels. Interestingly, high doses of aronia berry concentrate increased neuronal superoxide levels independent of paraquat, while at the same time decreasing hydrogen peroxide. Moreover, high-dose aronia berry concentrate potentiated paraquat-induced superoxide production and neuronal cell death. In summary, aronia berry concentrate at low doses restores the homeostatic redox environment of neurons treated with paraquat, while high doses exacerbate the imbalance leading to further cell death. Our findings support that moderate levels of aronia berry concentrate may prevent reactive oxygen species-mediated neurotoxicity.

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