Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy

• DOI: 10.1093/brain/aws143
• Publication Date: 2012-06-12T02:15:35Z
• Authors: Véronique Schaeffer; Isabelle Lavenir; Sefika Ozcelik; Markus Tolnay; David T. Winkler; Michel Goedert
• Keywords: Tauopathy; Tau protein; Autophagosome

The accumulation of insoluble proteins is a pathological hallmark several neurodegenerative disorders. Tauopathies are caused by the dysfunction and aggregation tau protein an impairment cellular degradation pathways may contribute to their pathogenesis. Thus, deficiency in autophagy can cause neurodegeneration, while activation protective against some proteinopathies. Little known about role animal models human tauopathy. In present report, we assessed effects stimulation trehalose transgenic mouse model tauopathy, mutant P301S mouse, using biochemical immunohistochemical analyses. Neuronal survival was evaluated stereology. Autophagy activated brain, where number neurons containing inclusions significantly reduced, as amount protein. This reduction aggregates associated with improved neuronal cerebral cortex brainstem. We also observed decrease p62 protein, suggesting that it removal inclusions. Trehalose failed activate spinal cord, had no impact on level sarkosyl-insoluble tau. Accordingly, effect motor mice. Our findings provide direct evidence favour autophagy. Activation be worth investigating context therapies for tauopathies.