Back to Search
Start Over
Chaperone-Mediated Autophagy Markers in Parkinson Disease Brains
- Source :
- Archives of Neurology. 67
- Publication Year :
- 2010
- Publisher :
- American Medical Association (AMA), 2010.
-
Abstract
- Objective: To investigate chaperone-mediated autophagy in the pathogenesis of Parkinson disease (PD).Design: Postmortem observational study.Setting: University Department of Clinical Neuroscience, Institute of Neurology, University College London.Subjects: Postmortem samples from 7 PD, 6 Alzheimer disease (AD), and 8 control brains.Main Outcome Measure: Lysosomal-associated membrane protein 2A (LAMP2A) and heat shock cognate 70 (hsc70) protein levels were compared in the substantia nigra pars compacta and amygdala of PD, AD, and control brain samples. To provide insight into the turnover of alpha-synuclein, degradation pathways for this protein were studied in a dopaminergic cell line.Results: The expression levels of the chaperone-mediated autophagy proteins LAMP2A and hsc70 were significantly reduced in the substantia nigra pars compacta and amygdala of PD brains compared with age-matched AD and control brain samples. Lewy bodies in these regions contained autophagy-related proteins. We demonstrated that decreased LAMP2A levels in dopaminergic cell lines reduced chaperone-mediated autophagy activity and increased the half-life of alpha-synuclein.Conclusions: These findings suggest that there is reduced chaperone-mediated autophagy activity in the PD brain, provide evidence for the role of autophagy in PD pathogenesis and Lewy body formation, and suggest that this pathway may be a suitable therapeutic target in PD.
- Subjects :
- Male
medicine.medical_specialty
Substantia nigra
Biology
Statistics, Nonparametric
chemistry.chemical_compound
Chaperone-mediated autophagy
Arts and Humanities (miscellaneous)
Alzheimer Disease
Dopamine
Cell Line, Tumor
Lysosomal-Associated Membrane Protein 2
Internal medicine
Autophagy
medicine
Humans
RNA, Small Interfering
Cell Proliferation
Alpha-synuclein
Lewy body
Pars compacta
Neurodegeneration
HSC70 Heat-Shock Proteins
Brain
Lysosome-Associated Membrane Glycoproteins
Parkinson Disease
medicine.disease
Hemagglutinins
Endocrinology
Gene Expression Regulation
nervous system
chemistry
Postmortem Changes
alpha-Synuclein
Female
Neurology (clinical)
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 00039942
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Archives of Neurology
- Accession number :
- edsair.doi.dedup.....ac5862529979df49adc471c74317dc05