Hydroxynonenal adducts indicate a role for lipid peroxidation in neocortical and brainstem Lewy bodies in humans.
Multiple lines of evidence indicate that oxidative stress is a critical pathogenic factor in Parkinson disease (PD) and diffuse Lewy body disease (DLBD). Previously, we demonstrated increased levels of redox-active iron in Lewy bodies, and that Lewy bodies accumulate advanced glycation end-products. To further characterize the role of oxidative stress in diseases with Lewy body formation, we examined immunocytochemically eight cases of PD and five cases of DLBD for adducts of the lipid peroxidation adduct 4-hydroxy-2-nonenal, and for N(epsilon)-(carboxymethyl)lysine (CML). Our findings demonstrate immunolocalization of 4-hydroxynonenal and CML to Lewy bodies in PD and DLBD. These findings not only support prior studies indicating that lipid peroxidation is increased in patients with PD and DLBD but that oxidative damage may play a critical role in Lewy body formation.
Castellani
Rudy J
RJ
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Perry
George
G
Siedlak
Sandra L
SL
Nunomura
Akihiko
A
Shimohama
Shun
S
Zhang
Jing
J
Montine
Thomas
T
Sayre
Lawrence M
LM
Smith
Mark A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000502:physiology*; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D000447:Aldehydes; C027576:4-hydroxy-2-nonenal