Tau modifiers as therapeutic targets for Alzheimer's disease.
Fibrillogenesis is a major feature of Alzheimer's disease (AD) and other neurodegenerative diseases. Fibers are correlated with disease severity and they have been implicated as playing a direct role in disease pathophysiology. In studies of tau, instead of finding causality with tau fibrils, we found that tau is associated with reduction of oxidative stress. Biochemical findings show that tau oxidative modifications are regulated by phosphorylation and that tau found in neurofibrillary tangles is oxidatively modified, suggesting that tau is closely linked to the biology, not toxicity, of AD.
Liu
Quan
Q
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
Lee
Hyoung-gon
HG
Honda
Kazuhiro
K
Siedlak
Sandra L
SL
Harris
Peggy L R
PL
Cash
Adam D
AD
Zhu
Xiongwei
X
Avila
Jesús
J
Nunomura
Akihiko
A
Takeda
Atsushi
A
Smith
Mark A
MA
Perry
George
G
D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D006151:Guanosine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D018384:Oxidative Stress; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D000447:Aldehydes; D016875:tau Proteins; D006151:Guanosine; C046215:8-hydroxyguanosine; C027576:4-hydroxy-2-nonenal