Coenzyme q induces tau aggregation, tau filaments, and Hirano bodies.
Tau aggregation is a common feature of tauopathies such as Alzheimer disease (AD). In AD, tau assembles into fibrillar polymers; it may also be present in other aberrant aggregates, including Hirano bodies. The mechanisms leading to tau polymerization in vivo are not understood. In this study, we found that coenzyme Q (ubiquinone) facilitates tau aggregation after binding to tau molecules at the region of the tau molecule involved in self-assembly. Consequently, after tau-tau interactions, this region is masked in fibrillar tau polymers. Further in vitro studies showed that ubiquinone facilitates the interaction of tau protein with actin to form structures that are morphologically similar to Hirano bodies. Finally, studies in AD brains show that Hirano bodies react with an antibody raised against ubiquinone, indicating that ubiquinone is a component of Hirano bodies. Taken together, the in vitro models and findings in AD suggest that in the presence of ubiquinone, Hirano bodies may result from the interaction of actin and other proteins, including tau.
Santa-Mara
Ismael
I
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid, Spain.
Santpere
Gabriel
G
MacDonald
Michael J
MJ
Gomez de Barreda
Elena
E
Hernandez
Felix
F
Moreno
Francisco J
FJ
Ferrer
Isidro
I
Avila
Jesús
J
D000199:Actins / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018977:Micronutrients / Q000378:metabolism / Q000494:pharmacology; D016253:Microscopy, Immunoelectron; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D014451:Ubiquinone / Q000378:metabolism* / Q000494:pharmacology; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism*
D000199:Actins; D018977:Micronutrients; D009498:Neurotoxins; D011108:Polymers; D016875:tau Proteins; D014451:Ubiquinone