Atypical protein kinase C in neurodegenerative disease II: PKCiota/lambda in tauopathies and alpha-synucleinopathies.
To study the role of atypical protein kinase C (aPKC) in neurodegenerative disease, we investigated the distribution of PKCiota/lambda, an aPKC isoform, in a variety of tauopathies and alpha-synucleinopathies. Immunohistochemical study revealed PKCiota/lambda within tau-positive neurofibrillary inclusions in Alzheimer disease (AD), progressive supranuclear palsy, corticobasal degeneration (CBD), and Pick disease (PiD), within alpha-synuclein-positive Lewy bodies in idiopathic Parkinson disease and dementia with Lewy bodies, as well as within glial inclusions in multisystem atrophy. We also observed PKCiota/lambda label of actin-rich Hirano bodies in AD, PiD, and elderly individuals. Double immunolabeling and fluorescence resonance energy transfer demonstrated close physical association between PKCiota/lambda and phospho-tau or alpha-synuclein in some neurofibrillary tangles and Lewy bodies. Furthermore, PKCiota/lambda colocalized with p62, a chaperone protein that binds to both aPKC and ubiquitin, in most of these inclusions. PKCiota/lambda also closely associated with the inactivated form of glycogen synthase kinase-3beta, GSK-3beta[ser9]. Together, these findings suggest that PKCiota/lambda may play a role in common mechanisms involving the pathogenesis of neurodegenerative disease.
Shao
Charles Y
CY
Department of Pathology , State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
Crary
John F
JF
Rao
Chandrakant
C
Sacktor
Todd C
TC
Mirra
Suzanne S
SS
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D007527:Isoenzymes; D051844:alpha-Synuclein; D016875:tau Proteins; D011493:Protein Kinase C