Quinones facilitate the self-assembly of the phosphorylated tubulin binding region of tau into fibrillar polymers.
The fragment of tau containing the first and third tubulin-binding motifs, involved in self-assembly of tau, was phosphorylated by protein kinase A (PKA). In the presence of hydroxynonenal (HNE) or in the presence of quinones such as juglone, 2,3-dimethoxy-5-methyl-1,4-benzoquinone (coenzyme Q(0) or DMM), or menadione, the polymerization of this phosphorylated tau fragment is catalyzed, whereas polymerization of the unmodified fragment takes place in a lesser extent. The quinones coenzyme Q(0) and menadione are found in every cell, including neural cells, and may interact with tau protein to facilitate its assembly into filamentous structures. These tau filaments, assembled in the presence of quinones, have a fibrillar morphology very similar to that of paired helical filaments present in the brains of patients with Alzheimer's disease.
Santa-María
Ismael
I
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Hernández
Félix
F
Martín
Concepción Pérez
CP
Avila
Jesús
J
Moreno
Francisco J
FJ
D020816:Amino Acid Motifs / Q000187:drug effects; D000595:Amino Acid Sequence; D016227:Benzoquinones / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009285:Naphthoquinones / Q000494:pharmacology; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011809:Quinones / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010837:Vitamin K 1 / Q000494:pharmacology; D024483:Vitamin K 3 / Q000494:pharmacology; D016875:tau Proteins / Q000302:isolation & purification / Q000378:metabolism*
D016227:Benzoquinones; D009285:Naphthoquinones; D010446:Peptide Fragments; D011108:Polymers; D011809:Quinones; D011994:Recombinant Proteins; D014404:Tubulin; D016875:tau Proteins; D014451:Ubiquinone; C060262:2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone; C109863:ubiquinone-O; D024483:Vitamin K 3; D010837:Vitamin K 1; D017868:Cyclic AMP-Dependent Protein Kinases; C005090:lawsone; C005134:juglone