Parkinson's disease-associated parkin colocalizes with Alzheimer's disease and multiple sclerosis brain lesions.
Parkin is implicated in the pathogenesis of Parkinson's disease. Furthermore, parkin targets misfolded proteins for degradation and protects cells against various forms of cellular stress, including unfolded-protein and oxidative stress. This points towards a protective role of parkin in neurological disorders in which these stressors are implicated, including Alzheimer's disease (AD) and multiple sclerosis (MS). Here, we assessed parkin distribution in AD and MS brain tissue using immunohistochemistry. In AD brains, parkin colocalized with classic senile plaques and amyloid-laden vessels as well as astrocytes associated with both lesions. Similarly, we observed enhanced astrocytic parkin immunoreactivity in MS lesions, particularly in inflammatory lesions. Furthermore, parkin mRNA expression was increased in an astrocytoma cell line after free radical exposure. Our data indicate that parkin is upregulated in AD and MS brain tissue and might represent a defense mechanism to counteract stress-induced damage in AD and MS pathogenesis.
Witte
Maarten E
ME
Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. m.witte@vumc.nl
Bol
John G J M
JG
Gerritsen
Wouter H
WH
van der Valk
Paul
P
Drukarch
Benjamin
B
van Horssen
Jack
J
Wilhelmus
Micha M M
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005609:Free Radicals / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000682:Amyloid; D005609:Free Radicals; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein