Atypical protein kinase C in neurodegenerative disease II: PKCiota/lambda in tauopathies and alpha-synucleinopathies.

Abstract

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.

• Authors: Charles Y Shao, John F Crary, Chandrakant Rao, Todd C Sacktor, Suzanne S Mirra
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 65 Issue 4 Pg. 327-35 (Apr 2006) ISSN: 0022-3069 [Print] England
• PMID: 16691114 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• alpha-Synuclein
• tau Proteins
• Protein Kinase C

Topics

• Aged
• Aged, 80 and over
• Brain (metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• Inclusion Bodies (metabolism)
• Isoenzymes (metabolism)
• Male
• Middle Aged
• Neurodegenerative Diseases (metabolism, pathology)
• Protein Kinase C (metabolism)
• alpha-Synuclein (metabolism)
• tau Proteins (metabolism)