Cerebellar degeneration-related autoantigen 1 (CDR1) gene expression in Alzheimer’s disease

Bosco, Paolo; Spada, Rosario S.; Caniglia, Salvatore; Salluzzo, Maria Grazia; Salemi, Michele

doi:10.1007/s10072-014-1805-6

Cited by 8 publications

(6 citation statements)

References 7 publications

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“…Costaining with anti-parvalbumin, a marker for stellate and basket cells, showed that CDR1 was also present in these cells (Celio 1990;Chen et al 1990). Moreover, CDR1 over-expression was reported in patients with Alzheimer disease (Bosco et al 2014) and a role in the Amyloid aggregation has been demonstrated (Ruiz-Zamora et al 2019). Different fibrillogenic hotspots have recently been identified at the CDR1 and βstrand C of the protein, thus likely suggesting a functional role in the central nervous system.…”

Section: Discussionmentioning

confidence: 98%

“…CDR1 over-expression has been demonstrated in prostate cancer cell lines (Salemi et al 2014). Interestingly, CDR1 has been found over-expressed in patients with Alzheimer's disease compared to controls, thus pointing to this gene a possible role in Alzheimer's disease process (Bosco et al 2014). It is not known whether the CDR1 gene expression is altered in DS patients.…”

Section: Introductionmentioning

confidence: 99%

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Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Salemi

Rappazzo

Ridolfo³

et al. 2020

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Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from lack of disjunction of sister chromatids of human chromosome 21 or not partial disjunction of chromosome 21 (Hsa21), usually during maternal meiosis. The expression of genes in chromosome 21 is very complex and many other genes in other chromosomes can play a role in DS. The protein encoded by the Cerebellar degeneration-related autoantigen 1 (CDR1) gene has been identified in patients with paraneoplastic cerebellar degeneration. Transcriptome studies show CDR1 expression in tumor cell lines and leukocytes of normal subjects and patients with Alzheimer's disease. We investigated CDR1 expression in cultured fibroblasts of DS patients compared with normal subjects. The study of CDR1 mRNA was performed with qRT-PCR. Immunofluorescence and Western blot were used for the analysis of the CDR1 protein. Our data show that both CDR1 mRNA and protein are expressed in human fibroblasts and that the CDR1 gene is down-regulated in DS fibroblasts compared to controls. These data suggest a role for CDR1 in DS phenotype.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Salemi

Rappazzo

Ridolfo³

et al. 2020

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“…Higher than normal levels of CDR1as have been reported in several cancers including colorectal (17), gastric (18), and liver (19). CDR1 mRNA is present at increased levels in patients with Alzheimer's disease (20) and prion disease (21), and decreased levels of CDR1 mRNA are observed in patients with Huntington's disease (22).…”

Section: Introductionmentioning

confidence: 98%

Subcellular Localization of Cerebellar Degeneration-Related Protein 1

Solheim

Kråkenes

Totland³

et al. 2020

Preprint

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Abstract Background: Cerebellar degeneration-related protein 1 (CDR1) is associated with paraneoplastic cerebellar degeneration – an autoimmunedisease characterized by neurodegeneration in the cerebellum. Paraneoplastic syndromes are believed to be triggered by ectopic tumour expression of neuronal proteins. The CDR1 protein is expressed by neurons in the cerebellar cortex and in certain cancers. In this study, we characterized the subcellular localization of CDR1 to help delineate potential functions in cancer cells and neurons. Methods: Ovarian cancer cells, cerebellar sections, and Purkinje cells in culture were immunostained and imaged by super-resolution stimulated emission depletion microscopy and potential interaction partners were investigated using a proximity ligation assay. Results: CDR1 was localized to the mitochondria in cancer cells and was colocalized with proteins of the outer mitochondrial membrane. Using a proximity ligation assay, we discovered that CDR1 interacts with mitofusin 1 – a transmembrane GTPase involved in mitochondrial fusion – in both cancer cells and rat cerebellum. CDR1 also colocalized with intermediate filaments, including vimentin, in cancer cells and with neurofilaments in human cerebellum. Conclusion: The dual localization to mitochondria and intermediate filaments as well as colocalization with key proteins involved in mitochondrial dynamics suggest that CDR1 is involved in the subcellular distribution of mitochondria in cells.

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“…Furneux et al found that CDR1 protein was specifically expressed in Purkinje cells in the cerebellum and that CDR1 antibodies recognized a band of approximately 34 kDa in a patient with PCD and breast tumor, but not in a patient with breast tumor without PCD [ 7 ]. The association between CDR1 and ovarian and breast cancer and PCD is not well established, but dysregulation of CDR1 has been associated with other neurological diseases like Huntington’s and Alzheimer’s disease [ 12 , 13 ], and various cancers like prostate cancer and glioblastoma [ 14 , 15 ]. Recently, it was reported that the antisense strand of CDR1 ( CDR1-AS , also known as ciRS-7 ) is transcribed into a circular exonic RNA with a miR-7 sponge function that stabilizes CDR1 mRNA [ 16 - 18 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer

et al. 2018

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Cerebellar degeneration related protein 1 (CDR1) is expressed in the cerebellum, and CDR1 antibodies have been associated with paraneoplastic cerebellar degeneration (PCD). In this study, we examined CDR1 expression in cerebellum and in ovarian and breast tumors, as well as the intracellular localization of CDR1 in cancer cells in culture. CDR1 was strongly expressed in the cytosol and dendrites of Purkinje cells and in interneurons of the molecular layer in cerebellum. CDR1 was also present in ovarian and breast tumors, as well as in ovarian and breast cancer cell lines, but was not present in normal breast or ovarian tissue. In cells overexpressing CDR1, CDR1 localized close to the plasma membrane in a polarized pattern at one edge. CDR1 was strongly expressed on the outer surface, apparently in filopodias or lamellipodias, in cells endogenously expressing CDR1. Overexpression of CDR1 showed a 37 and a 45 kDa band in western blot. The 37-kDa isoform was present in 16 ovarian cancer lysates, while the 45-kDa isoform was only found in three ovarian cancer patients. The presence of CDR1 in ovarian cancer was not associated with PCD. CDR1 antibodies were only found in serum from one patient with PCD and ovarian tumor with metastases. Therefore, CDR1 is probably not a marker for PCD. However, CDR1 may be associated with cell migration and differentiation.

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Cerebellar degeneration-related autoantigen 1 (CDR1) gene expression in Alzheimer’s disease

Cited by 8 publications

References 7 publications

Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Cerebellar degeneration-related protein 1 expression in fibroblasts of patients affected by down syndrome

Subcellular Localization of Cerebellar Degeneration-Related Protein 1

Expression of the onconeural protein CDR1 in cerebellum and ovarian cancer

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