Abstract
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.
Highlights
Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau
We have previously shown that CBL ameliorates the Rockenstein et al BMC Neurosci (2015) 16:85 neurodegenerative pathology in amyloid precursor protein (APP) transgenic models of Alzheimer’s disease (AD) [12,13,14,15] as well as in models of tauopathy expressing four-repeat tau (4R) tau [16, 17]
This was accompanied by reductions in the neurodegenerative pathology in both groups and by improvements in the behavioral deficits in the younger group
Summary
Tauopathies 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 CerebrolysinTM (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick’s disease over expressing 3R tau. Tau is a major neuronal cytoskeletal protein encoded by an alternatively spliced gene (MAPT) present on chromosome 17 (MAPT) [1]. Pick’s disease is a rare neurodegenerative disorder associated with dementia and fronto-temporal lobar degeneration [6]. There are sporadic and familial forms and mutations in MAPT account for the majority of these cases [7,8,9,10]
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