Neurotoxic dopamine quinone facilitates the assembly of tau into fibrillar polymers.
Aberrant aggregation of microtubule associated protein tau is the main characteristic of different disorders known as tauopathies. Different compounds have been described to facilitate tau aberrant aggregation. In this work, we demonstrate that oxidized products of dopamine (neurotoxic dopamine quinone), a neurotransmitter involved in Parkinson's disease, promote tau polymerization. Curiously, neurons expressing dopamine (substantia nigra) show a low content of tau protein and seldom have tau aggregation in tauopathies. In non-dopaminergic neurons, quinone oxidation products may be involved in tau polymerization. These results support a link between oxidative damage and the onset of tauopathies.
Santa-María
Ismael
I
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Hernández
Félix
F
Smith
Mark A
MA
Perry
George
G
Avila
Jesús
J
Moreno
Francisco J
FJ
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D016253:Microscopy, Immunoelectron; D009447:Neuroblastoma / Q000378:metabolism; D011108:Polymers / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism*
D016227:Benzoquinones; D006873:Hydroquinones; D011108:Polymers; D016875:tau Proteins; C004532:quinone; C104705:dopamine quinone; D004298:Dopamine; C031927:hydroquinone