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PMID: 10688892 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 6 ·2000-03-14 ·Pages 2875-80

Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, Evan GI, Agid Y, Hirsch EC

Abstract

Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3 immunohistochemistry on the postmortem human brain, we observed a positive correlation between the degree of neuronal loss in dopaminergic (DA) cell groups affected in the mesencephalon of PD patients and the percentage of caspase-3-positive neurons in these cell groups in control subjects and a significant decrease of caspase-3-positive pigmented neurons in the substantia nigra pars compacta of PD patients compared with controls that also could be observed in an animal model of PD. This suggests that neurons expressing caspase-3 are more sensitive to the pathological process than those that do not express the protein. In addition, using an antibody raised against activated caspase-3, the percentage of active caspase-3-positive neurons among DA neurons was significantly higher in PD patients than in controls. Finally, electron microscopy analysis in the human brain and in vitro data suggest that caspase-3 activation precedes and is not a consequence of apoptotic cell death in PD.

MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology Aged Aged, 80 and over Animals Apoptosis Blotting, Western Brain/enzymology,ultrastructure Caspase 3 Caspases/biosynthesis,physiology Cells, Cultured Dopamine/metabolism Dopamine Agents/pharmacology Enzyme Activation Humans Immunohistochemistry Male Mesencephalon/enzymology Mice Mice, Inbred C57BL Neurons/enzymology,ultrastructure Parkinson Disease/enzymology,metabolism Rats Substantia Nigra/enzymology Tissue Distribution Ventral Tegmental Area/enzymology
Chemicals
Dopamine Agents 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine CASP3 protein, human Casp3 protein, mouse Casp3 protein, rat Caspase 3 Caspases Dopamine
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Hartmann A
Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
Hunot S
Michel P P
Muriel M P
Vyas S
Faucheux B A
Mouatt-Prigent A
Turmel H
Srinivasan A
Ruberg M
Evan G I
Agid Y
Hirsch E C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.040556597
Published
2000-03-14
Pages
2875-80
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16023
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.040556597 PMC Full Text View journal details
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