tau reduction does not prevent motor deficits in two mouse models of parkinsons diseaseτ削减赤字并不妨碍电动机在两个帕金森病小鼠模型.pdf

Tau Reduction Does Not Prevent Motor Deficits in Two Mouse Models of Parkinson’s Disease 1,2 1¤ 3 1,4 Meaghan Morris , Akihiko Koyama , Eliezer Masliah , Lennart Mucke * 1 Gladstone Institute of Neurological Disease, San Francisco, California, United States of America, 2 Biochemistry, Cellular and Molecular Biology Graduate Program, Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3 Departments of Neuroscience and Pathology, University of California San Diego, La Jolla, California, United States of America, 4 Department of Neurology, University of California San Francisco, San Francisco, California, United States of America Abstract Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype a-synuclein. Both models were evaluated on Tau+/+, Tau+/– and Tau–/– backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau r