Differential sensitivity to proteolysis by brain calpain of adult human tau, fetal human tau and PHF-tau.
Reduced turn-over of tau by calpains is a possible mechanism to facilitate the incorporation into paired helical filaments (PHFs) in Alzheimer's disease. The present study shows that the differently phosphorylated fetal tau isoforms are all rapidly proteolysed to an equal extent by human brain m-calpain. This result argues against the hypothesis that this type of fetal phosphorylation is involved in reducing tau turn-over by calpain in Alzheimer's disease. Adult and fetal tau fragments in vitro generated by m-calpain, but not trypsin, cathepsin D or chymotrypsin resemble the post-mortem in situ degradation patterns, suggesting a possible role for calpains in tau metabolism in vivo. Tau incorporated into PHFs was considerably more resistant to proteolysis by calpain which can help to explain the persistence of these structures in Alzheimer's disease.
Mercken
M
M
Laboratories for Molecular Neuroscience, McLean Hospital, Belmont, MA 02178, USA.
Grynspan
F
F
Nixon
R A
RA
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D005326:Fetal Proteins; D016875:tau Proteins; D010450:Endopeptidases; D002154:Calpain