Format

Send to

Choose Destination
See comment in PubMed Commons below
Acta Neuropathol. 2005 Dec;110(6):547-56. Epub 2005 Oct 14.

Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies.

Author information

1
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 700-8558, Okayama, Japan.

Abstract

Lithium, a widely used drug for treating affective disorders, is known to inhibit glycogen synthase kinase-3 (GSK-3), which is one of the major tau kinases. Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation. We tested this hypothesis and showed that long-term administration of lithium at relatively low therapeutic concentrations to transgenic mice that recapitulate Alzheimer's disease (AD)-like tau pathologies reduces tau lesions, primarily by promoting their ubiquitination rather than by inhibiting tau phosphorylation. These findings suggest novel mechanisms whereby lithium treatment could ameliorate tauopathies including AD. Because lithium also has been shown to reduce the burden of amyloid-beta pathologies, it is plausible that lithium could reduce the formation of both amyloid plaques and tau tangles, the two pathological hallmarks of AD, and thereby ameliorate the behavioral deficits in AD.

PMID:
16228182
DOI:
10.1007/s00401-005-1087-4
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Support Center