Atypical protein kinase C in neurodegenerative disease II: PKCι/λ in tauopathies and α-synucleinopathies

To study the role of atypical protein kinase C (aPKC) in neurodegenerative disease, we investigated the distribution of PKCι/λ, an aPKC isoform, in a variety of tauopathies and α-synucleinopathies. Immunohistochemical study revealed PKCι/λ within tau-positive neurofibrillary inclusions in Alzheimer disease (AD), progressive supranuclear palsy, corticobasal degeneration (CBD), and Pick disease (PiD), within α-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 PKCι/λ label of actin-rich Hirano bodies in AD, PiD, and elderly individuals. Double immunolabeling and fluorescence resonance energy transfer demonstrated close physical association between PKCι/λ and phospho-tau or α-synuclein in some neurofibrillary tangles and Lewy bodies. Furthermore, PKCι/λ colocalized with p62, a chaperone protein that binds to both aPKC and ubiquitin, in most of these inclusions. PKCι/λ also closely associated with the inactivated form of glycogen synthase kinase-3β, GSK-3β[ser9]. Together, these findings suggest that PKCι/λ may play a role in common mechanisms involving the pathogenesis of neurodegenerative disease.