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Cited by 554

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Chaperone-Mediated Autophagy Markers in Parkinson Disease Brains

Alvarez-Erviti, Lydia, Rodriguez-Oroz, Maria C., Cooper, J. Mark, Caballero, Cristina, Ferrer, Isidro, Obeso, Jose A., Schapira, Anthony H. V.·2010·Archives of Neurology

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 α-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 α-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.

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Crossref · 10.1001/archneurol.2010.198

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Metadata

Authors
Alvarez-Erviti, L., Rodriguez-Oroz, M. C., Cooper, J. M., Caballero, C., Ferrer, I., Obeso, J. A., & Schapira, A. H. V.
Venue
Archives of Neurology
Published
2010-12-01
Volume
67
Issue
12
Pages
1464-72
ISSN
0003-9942 (ISSN-L)
OpenAlex
W2027096397
Cited by
554
References
8
FWCI
18.58
Type
journal article
Language
en
Open access
closed

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