PHF-like tau phosphorylation in mammalian hibernation is not associated with p25-formation.
In Alzheimer's disease and related disorders, hyperphosphorylation of tau is associated with an increased activity of cyclin dependent kinase 5 (cdk5). Elevated cdk5 activity is thought to be due to the formation of p25 and thereby represents a critical element in the dysregulation of tau phosphorylation under pathological conditions. However, there is still a controversy regarding the correlation of p25 generation and tau pathology. Recently, we demonstrated physiological, paired helical filament-like tau phosphorylation that reversibly occurs in hibernating mammals. Here we used this model to test whether the tau phosphorylation in hibernation is associated with the formation of p25. Analysing brain material of arctic ground squirrels and Syrian hamsters we found no evidence for a hibernation dependent generation of p25. Hence, we suppose that phosphorylation of tau does not require the formation of p25. Instead we suggest that the truncation of p35 to p25 represents a characteristic of pathological alterations and may contribute to aggregation and deposition of hyperphosphorylated tau.
Stieler
Jens Thorsten
JT
Department of Molecular and Cellular Mechanisms of Neurodegeneration, Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109, Leipzig, Germany. spitz@uni-leipzig.de
Bullmann
Torsten
T
Kohl
Franziska
F
Barnes
Brian M
BM
Arendt
Thomas
T
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D006224:Cricetinae; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D005260:Female; D006605:Hibernation; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D012589:Sciuridae; D016875:tau Proteins / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D011108:Polymers; C089495:neuronal Cdk5 activator (p25-p35); C506479:poly(1-hydroxymethylethylene hydroxymethylformal); D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5