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http://purl.uniprot.org/citations/19788048http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19788048http://www.w3.org/2000/01/rdf-schema#comment"

Background

Recent studies highlight the role of endoplasmic reticulum (ER) stress and aberrant protein degradation in the pathogenesis of neurodegenerative disorders. Herp which is encoded by the HERPUD 1 (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1) gene is a stress-response protein localized in the ER membrane of neurons and other cell types. Herp has been suggested to improve ER-folding, decrease ER protein load, and participate in ER-associated degradation (ERAD) of proteins.

Methods

Based on microarray expression profiling results we have predicted an increased expression of HERPUD1 in the substantia nigra of Parkinson's disease (PD) patients. We have now used brain tissue of some of the same and additional cases of sporadic PD to localize Herp mRNA and protein in individual cell types.

Results

We found expression of Herp in neurons and in glial cells including astrocytes. These findings were corroborated by in situ hybridization. Accumulation of Herp protein was also detected in the core of Lewy bodies suggesting a role in their formation. Hierarchical clustering analysis identified TWINKLE (PEO1) as the gene whose expression profile was most similar to that of Herp across the PD cohort.

Conclusions

The nigral glial cells that expressed Herp at a high level resembled TUNEL-positive glia. While some of these cells likely undergo degeneration, the strong up-regulation of Herp in glia could help to explain the inflammation-like changes observed in PD ("neuroinflammation") as it has been shown that the unfolded protein response serves as an important regulator of inflammatory genes in other organs."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Wang B."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Cheetham M.E."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Michael G.J."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Graeber M.B."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Moran L.B."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Pearce R.K."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Novoselov S."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/author"Slodzinski H."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/name"Clin Neuropathol"xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/pages"333-343"xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/title"Homocysteine-induced endoplasmic reticulum protein (herp) is up-regulated in parkinsonian substantia nigra and present in the core of Lewy bodies."xsd:string
http://purl.uniprot.org/citations/19788048http://purl.uniprot.org/core/volume"28"xsd:string
http://purl.uniprot.org/citations/19788048http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19788048
http://purl.uniprot.org/citations/19788048http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19788048
http://purl.uniprot.org/uniprot/Q15011#attribution-604737654AC22B36BB4BA171DC85B663http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/19788048
http://purl.uniprot.org/uniprot/Q15011#attribution-965705520524546CC31DA3F92B281FC9http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/19788048