Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies

BMC Neuroscience

Research Article

Hemma Brandstaetter¹  Stefan Winter¹  Dieter Meier¹  Michael Mante²  Anthony Adame²  Edward Rockenstein²  Kiren Ubhi²  Jazmin Florio²  Eliezer Masliah³ 

[1] Clinical Research and Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria;Department of Neurosciences, University of California, La Jolla, 92093-0624, San Diego, CA, USA;Department of Neurosciences, University of California, La Jolla, 92093-0624, San Diego, CA, USA;Department of Pathology, University of California, La Jolla, San Diego, CA, USA;

关键词: 3 repeat Tau;    Pick’s disease;    Cerebrolysin;    Neuronal loss;    Transgenic;   

DOI  :  10.1186/s12868-015-0218-7

 received in 2015-07-03, accepted in 2015-11-13,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundTauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick’s disease and Alzheimer’s disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick’s disease over expressing 3R tau.ResultsMice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3–6 month group.ConclusionTaken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau.

【 授权许可】

CC BY   
© Rockenstein et al. 2015