Skip to Content
Merck
  • Clioquinol rescues Parkinsonism and dementia phenotypes of the tau knockout mouse.

Clioquinol rescues Parkinsonism and dementia phenotypes of the tau knockout mouse.

Neurobiology of disease (2015-03-23)
Peng Lei, Scott Ayton, Ambili Thoppuvalappil Appukuttan, Irene Volitakis, Paul A Adlard, David I Finkelstein, Ashley I Bush
ABSTRACT

Iron accumulation and tau protein deposition are pathological features of Alzheimer's (AD) and Parkinson's diseases (PD). Soluble tau protein is lower in affected regions of these diseases, and we previously reported that tau knockout mice display motor and cognitive behavioral abnormities, brain atrophy, neuronal death in substantia nigra, and iron accumulation in the brain that all emerged between 6 and 12 months of age. This argues for a loss of tau function in AD and PD. We also showed that treatment with the moderate iron chelator, clioquinol (CQ) restored iron levels and prevented neuronal atrophy and attendant behavioral decline in 12-month old tau KO mice when commenced prior to the onset of deterioration (6 months). However, therapies for AD and PD will need to treat the disease once it is already manifest. So, in the current study, we tested whether CQ could also rescue the phenotype of mice with a developed phenotype. We found that 5-month treatment of symptomatic (13 months old) tau KO mice with CQ increased nigral tyrosine hydroxylase phosphorylation (which induces activity) and reversed the motor deficits. Treatment also reversed cognitive deficits and raised BDNF levels in the hippocampus, which was accompanied by attenuated brain atrophy, and reduced iron content in the brain. These data raise the possibility that lowering brain iron levels in symptomatic patients could reverse neuronal atrophy and improve brain function, possibly by elevating neurotrophins.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
Hydrogen peroxide solution, contains potassium stannate as inhibitor, 30-32 wt. % in water, semiconductor grade, 99.999% trace metals basis
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
Hydrogen peroxide solution, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, meets USP testing specifications
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, ACS reagent
Sigma-Aldrich
Hydrogen peroxide solution, purum p.a., ≥35% (RT)
Sigma-Aldrich
Hydrogen peroxide solution, 50 wt. % in H2O, stabilized
Sigma-Aldrich
Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Sucrose, ≥99.5% (GC), Grade II, suitable for plant cell culture
Sigma-Aldrich
Sucrose, Grade I, ≥99% (GC), suitable for plant cell culture
Sigma-Aldrich
Sucrose, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioXtra
Sigma-Aldrich
Sucrose, meets USP testing specifications
Sigma-Aldrich
MES, low moisture content, ≥99% (titration)
Sigma-Aldrich
Sucrose, ACS reagent
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
Sigma-Aldrich
MES solution, BioUltra, for molecular biology, 0.5 M in H2O