Cortical and hippocampal neurons from truncated tau transgenic rat express multiple markers of neurodegeneration.
Transition of protein tau from physiologically unfolded to misfolded state represent enigmatic step in the pathogenesis of tauopathies including Alzheimer's disease (AD). Major molecular events playing role in this process involve truncation and hyperphosphorylation of tau protein, which are accompanied by redox imbalance followed by functional deterioration of neuronal network. Recently we have developed transgenic rat model showing that expression of truncated tau causes neurofibrillary degeneration similar to that observed in brain of AD sufferers. Consequently we tested cortical and hippocampal neuronal cultures extracted from this model as a convenient tool for development of molecules able to target the mechanisms leading to and/or enhancing the process of neurodegeneration. Here we document three major pathological features typical for tauopathies and AD in cortical and hippocampal neurons from transgenic rat in vitro. First, an increased accumulation of human truncated tau in neurons; second, the hyperphosphorylation of truncated tau on the epitopes characteristic of AD (Ser202/Thr205 and Thr231); and third, increased vulnerability of the neurons to nitrative and oxidative stress. Our results show that primary neurons expressing human truncated tau could represent a cellular model for targeting tau related pathological events, namely, aberrant tau protein accumulation, tau hyperphosphorylation, and oxidative/nitrative damage. These characteristics make the model particularly suitable for detailed study of molecular mechanisms of tau induced neurodegeneration and easily applicable for drug screening.
Filipcik
Peter
P
Institute of Neuroimmunology, Center of Excellence, SAV, 845 10 Bratislava, Slovak Republic. peter.filipcik@savba.sk
Cente
Martin
M
Krajciova
Gabriela
G
Vanicky
Ivo
I
Novak
Michal
M
D000818:Animals; D015415:Biomarkers; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D055647:Rats, Transgenic; D024801:Tauopathies / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
D015415:Biomarkers; D016875:tau Proteins