S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.

Brain : a Journal of Neurology
Weizhen Ye, Stacy W Blain

Abstract

A major phenotype seen in neurodegenerative disorders is the selective loss of neurons due to apoptotic death and evidence suggests that inappropriate re-activation of cell cycle proteins in post-mitotic neurons may be responsible. To investigate whether reactivation of the G1 cell cycle proteins and S phase entry was linked with apoptosis, we examined homocysteine-induced neuronal cell death in a rat cortical neuron tissue culture system. Hyperhomocysteinaemia is a physiological risk factor for a variety of neurodegenerative diseases, including Alzheimer's disease. We found that in response to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nucleus, and p27 levels decreased. Both cyclin-dependent kinases 4 and 2 regained catalytic activity, the G1 gatekeeper retinoblastoma protein was phosphorylated and DNA synthesis was detected, suggesting transit into S phase. Double-labelling immunofluorescence showed a 95% co-localization of anti-bromodeoxyuridine labelling with apoptotic markers, demonstrating that those cells that entered S phase eventually died. Neurons could be protected from homocysteine-induced death by methods that inhibited G1 phase progression, including down-regulation...Continue Reading

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Citations

Feb 22, 2011·Apoptosis : an International Journal on Programmed Cell Death·Weizhen Ye, Stacy W Blain
Sep 13, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sabrina AbsalonAnna M Krichevsky
Jan 15, 2013·Brain Research·Claudia BrunnliebMarcus Heldmann
May 14, 2011·Movement Disorders : Official Journal of the Movement Disorder Society·Maria MilenkovaThomas F Münte
Jun 10, 2015·Journal of the Neurological Sciences·Zhen TaoYumin Luo
Sep 4, 2012·Neurobiology of Disease·Michel EngelnPierre-Olivier Fernagut
Jul 20, 2016·Annual Review of Nutrition·A David Smith, Helga Refsum
Jul 13, 2018·Journal of Virology·Yonggang PeiErle S Robertson
Oct 21, 2020·Essays in Biochemistry·Yu SunGabriel Balmus

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