Protein kinase C anchoring deficit in postmortem brains of Alzheimer's disease patients.
Protein kinase C (PKC) has been implicated in the pathophysiology of Alzheimer's disease (AD). The levels of particular isoforms and the activation of PKC are reduced in postmortem brain cortex of AD subjects. Receptors for activated C kinase (RACK) are a family of proteins involved in anchoring activated PKCs to relevant subcellular compartments. Recent evidence has indicated that the impaired activation (translocation) of PKC in the aging brain is associated with a deficit in RACK1, the most well-characterized member of this family. The present study was conducted to determine whether alterations in RACK1 occurred in cortical areas where an impaired translocation of PKC has been demonstrated in AD. Here we report the presence of RACK1 immunoreactivity in human brain frontal cortex for the first time and demonstrate a decrease in RACK1 content in cytosol and membrane extracts in AD when compared with non-AD controls. By comparison, the levels of the RACK1-related PKCbetaII were not modified in the same membrane extracts. These observations add a new perspective in understanding the disease-associated defective PKC signal transduction and indicate that a decrease in an anchoring protein for PKC is an additional determinant of this deficit.
Battaini
F
F
Department of Neurosciences, University of Roma Tor Vergata, Rome, Italy.
Pascale
A
A
Lucchi
L
L
Pasinetti
G M
GM
Govoni
S
S
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011180:Postmortem Changes; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051381:Rats; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D012016:Reference Values
D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C070301:peptide I; D011493:Protein Kinase C; D064546:Protein Kinase C beta