TY - JOUR T1 - Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies. AU - Nakashima,Hanae, AU - Ishihara,Takeshi, AU - Suguimoto,Pilar, AU - Yokota,Osamu, AU - Oshima,Etsuko, AU - Kugo,Aki, AU - Terada,Seishi, AU - Hamamura,Takashi, AU - Trojanowski,John Q, AU - Lee,Virginia M-Y, AU - Kuroda,Shigetoshi, Y1 - 2005/10/14/ PY - 2005/07/07/received PY - 2005/08/23/accepted PY - 2005/08/23/revised PY - 2005/10/18/pubmed PY - 2006/5/6/medline PY - 2005/10/18/entrez SP - 547 EP - 56 JF - Acta neuropathologica JO - Acta Neuropathol VL - 110 IS - 6 N2 - 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. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/16228182/Chronic_lithium_treatment_decreases_tau_lesions_by_promoting_ubiquitination_in_a_mouse_model_of_tauopathies_ DB - PRIME DP - Unbound Medicine ER -