Effect of quinones on microtubule polymerization: a link between oxidative stress and cytoskeletal alterations in Alzheimer's disease.
Increases in the concentration of quinones, such as benzoquinone, in pathological processes mediated by oxidative imbalance play a role in the disorganization and disassembly of the microtubule network in both non-neural and neural cells. In this study, we show that the effects on microtubules appear to be a direct result of the action of the quinones on tubulin, the main component of microtubules, since tubulin modification by quinones, including benzoquinone and juglone, leads to aggregation into dimers and other oligomers. Therefore, quinones and quinone-mediated effects provide a mechanistic link between oxidative stress, microtubule disruption, neuronal dysfunction and death, i.e., key salient feature of Alzheimer's disease.
Santa-María
Ismael
I
Centro de Biología Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Smith
Mark A
MA
Perry
George
G
Hernández
Félix
F
Avila
Jesús
J
Moreno
Francisco J
FJ
D016475:3T3 Cells; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001704:Biopolymers / Q000096:biosynthesis*; D002470:Cell Survival; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009426:Netherlands; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011809:Quinones / Q000378:metabolism / Q000633:toxicity*; D014404:Tubulin / Q000378:metabolism* / Q000648:ultrastructure
D001704:Biopolymers; D011809:Quinones; D014404:Tubulin