Increase of cdk5 is related to neurofibrillary pathology in progressive supranuclear palsy.
BACKGROUND
Progressive supranuclear palsy (PSP) is characterized by a pure neurofibrillary tau pathology involving mainly basal ganglia and brainstem nuclei. In addition to a haplotype of the tau gene potentially favoring tau aggregation, lipoperoxidation has been shown to be associated with PSP tau pathology.


OBJECTIVE
To analyze cdk5/p35 complex, a kinase that regulates neurite outgrowth, as a potential cellular mechanism underlying tau phosphorylation in brain tissues from PSP and control cases and comparatively in cerebral cortex from subjects with AD.


METHODS
Cdk5/p35 protein levels and distribution were evaluated by immunoblotting and immunocytochemistry in brain regions from seven PSP, six AD, and seven control cases, with similar postmortem intervals.


RESULTS
Total cdk5 protein levels were significantly increased by more than threefold in PSP tissue and were augmented in PSP neurons, codistributed with tau immunoreactivity. P35, the regulatory subunit of cdk5, was degraded by postmortem proteolysis to the same extent in PSP, AD, and control tissues.


CONCLUSIONS
The proteolysis in vivo of p35, the regulatory subunit of the kinase, is not ascertainable because it is masked by its postmortem degradation. The study, however, indicates that in PSP, the alteration of cdk5 is different from that described in AD and suggests that the absence of amyloid beta protein deposition may account for the different pathways responsible for the same kinase activation.
Borghi
R
R
Department of Neuroscience, University of Genova, Italy.
Giliberto
L
L
Assini
A
A
Delacourte
A
A
Perry
G
G
Smith
M A
MA
Strocchi
P
P
Zaccheo
D
D
Tabaton
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000201:enzymology* / Q000473:pathology*; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases