Immunohistochemical localization of apoptosome-related proteins in Lewy bodies in Parkinson's disease and dementia with Lewy bodies.
Apoptotic stimuli induce the release of cytochrome c from the mitochondria to the cytosol, and this released cytochrome c promotes the formation of the apoptosome, which contains cytochrome c, Apaf-1 and caspase-9, resulting in the activation of caspase-9 and the promotion of apoptotic cell death. To investigate the role of the apoptosome in patients with Parkinson׳s disease (PD), we performed immunohistochemical studies on apoptosome-related proteins in formalin-fixed, paraffin-embedded sections from 8 normal subjects, 10 patients with PD and 5 patients with dementia with Lewy bodies (DLB). Furthermore, we performed double-labeling immunohistochemistry for cleaved caspase-9 and CD68 in some sections from 8 normal subjects and 10 patients with PD. In the substantia nigra and locus ceruleus from both control and PD cases, the somata and processes of melanin-containing neurons were immunostained for cytochrome c, Apaf-1 and caspase-9. In the same areas from the PD cases, brainstem-type Lewy bodies were also immunoreactive for cytochrome c, Apaf-1 and caspase-9, and cleaved caspase-9 immunoreactivity was detected in brainstem-type Lewy bodies and CD68-immunopositive microglia. In addition to brainstem-type Lewy bodies, cortical Lewy bodies were also immunoreactive for these apoptosome-related proteins in the frontal and temporal cortices from the DLB cases. Our results suggest that apoptosome formation accompanied by caspase-9 activation may occur in the substantia nigra and locus ceruleus in brains affected by PD, and that a mitochondria-dependent apoptotic pathway may be partially associated with the pathogenesis of PD.
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan; Department of Neurology, Seijinkai Rakusaishimizu Hospital, Kyoto, Japan. Electronic address: kawamoto@kuhp.kyoto-u.ac.jp.
Yasuhiro
Y
Kawamoto
Department of Neurology, Wakayama Medical University, Wakayama, Japan.
Hidefumi
H
Ito
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Takashi
T
Ayaki
Department of Neurology, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Ryosuke
R
Takahashi
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D053478:Apoptosomes / Q000378:metabolism*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053478:Apoptosomes; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053453:Caspase 9; D045304:Cytochromes c; C506592:APAF1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule
Apoptosome; Caspase-9; Lewy body; Mitochondria; Parkinson׳s disease