Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects

Autism is a severe neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic mechanisms may partially contribute to the pathogenesis of this disorder. Cathepsin D is the predominant lysosomal protease and is...

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Veröffentlicht in:Neuroscience Jg. 165; H. 2; S. 363 - 370
Hauptverfasser: Sheikh, A.M., Li, X., Wen, G., Tauqeer, Z., Brown, W.T., Malik, M.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Amsterdam Elsevier Ltd 20.01.2010
Elsevier
Schlagworte:
Adolescent
apoptosis
autism
Autistic Disorder - metabolism
Bcl-2
Biological and medical sciences
Blotting, Western
Brain - metabolism
Caspase 3 - metabolism
caspase-3
cathepsin D
Cathepsin D - metabolism
Cerebellum - metabolism
Child
Child, Preschool
Female
Frontal Lobe - metabolism
Fundamental and applied biological sciences. Psychology
Hippocampus - metabolism
Humans
Immunohistochemistry
inflammation
Male
Neurology
Neurons - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Vertebrates: nervous system and sense organs
Bcl-2
TGF
IL
cathepsin D
inflammation
apoptosis
TNF
autism
caspase-3
tumor necrosis factor
interleukin
transforming growth factor
Human
Enzyme
Cysteine endopeptidases
Central nervous system
Caspase
Inflammation
Protein
Encephalon
Peptidases
Cell death
Hydrolases
Aspartic endopeptidases
Cathepsin D
Apoptosis
ISSN:0306-4522, 1873-7544, 1873-7544
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Zusammenfassung:Autism is a severe neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic mechanisms may partially contribute to the pathogenesis of this disorder. Cathepsin D is the predominant lysosomal protease and is abundantly expressed in the brain. It plays an important role in regulation of cellular apoptosis and has been shown to mediate apoptosis induced by cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ. In this study, we examined the expression levels of cathepsin D in the autistic brain. We found that cathepsin D protein expression was significantly increased in the frontal cortex, in pyramidal and granule cells of the hippocampus, and in cerebellar neurons in autistic subjects as compared to controls. In addition, we found that the expression of the anti-apoptotic protein Bcl-2 was significantly decreased, while caspase-3, a critical executioner of apoptosis, was increased in the cerebellum of autistic subjects. Previously our studies have shown that Bcl-2 expression is decreased and the BDNF-Akt-Bcl-2 pathway is compromised in the frontal cortex of autistic subjects, which suggested that increased apoptosis may be involved in the pathogenesis of autism. Our current finding of decreased Bcl-2 and increased capase-3 in the cerebellum of autistic subjects further supports this suggestion. In addition, the finding of increased cathepsin D in the cerebellum of autistic subjects suggests that, through its regulation of apoptosis, the altered activities of cathepsin D in the autistic brain may play an important role in the pathogenesis of autism.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0306-4522
1873-7544
1873-7544
DOI:10.1016/j.neuroscience.2009.10.035