EMAIL THIS PAGE TO A FRIEND

Neurobiology of disease

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


PMID 25796563

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.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1405514
Anti-BDNF antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
B9186 Anti-Brain-derived Neurotrophic Factor antibody produced in chicken, affinity isolated antibody, lyophilized powder
SAB2501155
Anti-TH (C-terminal) antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2103892
Anti-TH, (N-terminal) antibody produced in rabbit, affinity isolated antibody
SAB2103911
Anti-TH, (N-terminal) antibody produced in rabbit, affinity isolated antibody
T8700 Anti-Tyrosine Hydroxylase antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution, sufficient for 10 blots
M3671
MES, low moisture content, ≥99% (titration)
C6H13NO4S
76039
MES solution, BioUltra, for molecular biology, 0.5 M in H2O
C6H13NO4S
SAB1402127
Monoclonal Anti-BDNF antibody produced in mouse, clone 1B10, purified immunoglobulin, buffered aqueous solution
B5050 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 35928.11, purified immunoglobulin, lyophilized powder
B9436 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 37141, purified immunoglobulin, lyophilized powder
B9561 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 35909, purified immunoglobulin, lyophilized powder
B9686 Monoclonal Anti-Brain-derived Neurotrophic Factor antibody produced in mouse, clone 37129, purified immunoglobulin, lyophilized powder