Neurodegenerative mechanisms in Alzheimer disease. A role for oxidative damage in amyloid beta protein precursor-mediated cell death

Molecular and Chemical Neuropathology
B L SopherG M Martin

Abstract

We have established a stably transformed human neuroblastoma cell line (MC65) that conditionally expresses a C-terminal derivative of the amyloid beta protein precursor (beta PP) termed S beta C (a fusion protein composed of the amino-17 and carboxyl-99 residues of beta PP). Conditional expression of S beta C (mediated by the withdrawal of tetracycline from the culture medium) induces pronounced nuclear DNA fragmentation and cytotoxicity in this cell line. These effects are enhanced by hyperoxygen and suppressed by hypooxygen and antioxidants. This cell line is relatively insensitive to the extracellular application of amyloid beta 25-35, and coculture experiments suggest that this cytotoxicity is mediated by an intracellular process. These findings suggest that the overexpression of the C-terminal domain of beta PP can disrupt normal cellular processes in these cells in such a way as to induce a directed (deoxyribonuclease-mediated) mechanism of cell death. This process appears to be modulated and/or mediated by a reactive oxygen specie(s) (ROS). Consistent with a role for ROS in the process of S beta C-mediated toxicity, we have found that the MC65 cell line is hypersensitive to oxidative stress and that it is this sensitivit...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Dec 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C D SmithW R Markesbery
Jan 15, 1992·Biochemical and Biophysical Research Communications·K FukuchiG M Martin
Oct 22, 1993·Cell·D M HockenberyS J Korsmeyer
Apr 24, 1995·Biochimica Et Biophysica Acta·K HensleyD A Butterfield
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·K HensleyD A Butterfield
Mar 1, 1994·Trends in Biochemical Sciences·G Haecker, D L Vaux
Sep 24, 1993·Annals of the New York Academy of Sciences·K FukuchiG M Martin
Dec 1, 1993·Journal of Cellular Physiology·L Hopp, C H Bunker
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·B N AmesT M Hagen
Jan 14, 1993·Nature·K FukuchiG M Martin

❮ Previous
Next ❯

Citations

Aug 29, 2012·Future Medicinal Chemistry·David Schubert, Pamela Maher
Oct 12, 2012·The American Journal of Clinical Nutrition·Elizabeth J Johnson
Oct 27, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Kathryn MullanGareth J McKay
Sep 10, 2019·Organic & Biomolecular Chemistry·Trapti AggarwalAkhilesh K Verma
Sep 6, 2002·Journal of Molecular Neuroscience : MN·Lee-Way JinGeorge M Martin
Jul 1, 1997·Reviews in the Neurosciences·M DragunowR L Faull
May 14, 2011·Phytotherapy Research : PTR·Suresh KumarEdward J Okello
Feb 19, 2016·Journal of Alzheimer's Disease : JAD·Nora E GrayPhilip F Copenhaver
Jan 10, 2018·Aging Cell·Joshua GoldbergDavid Schubert
May 13, 2017·Future Medicinal Chemistry·Eva RamosAlejandro Romero
Dec 19, 2019·Nutrients·Puja AgarwalMartha Clare Morris
Sep 2, 2003·Acta Paediatrica. Supplement·D K Rassin, K E Smith
Jul 1, 2020·Biopolymers·Chelladurai Karthikeyan BalavigneswaranNira Misra
Oct 8, 2020·Cell Death & Disease·Ling HuangAntonio Currais
Mar 17, 2000·Free Radical Biology & Medicine·R Liu, J Choi
Jan 8, 2013·ACS Medicinal Chemistry Letters·Kai LiuShijun Zhang
Aug 20, 2015·ACS Medicinal Chemistry Letters·Kai Liu, Shijun Zhang
Oct 18, 2013·Journal of Medicinal Chemistry·Michela RosiniCarlo Melchiorre
Sep 20, 2011·Biochimica Et Biophysica Acta·Thimmappa S Anekonda, Joseph F Quinn

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.