The role of chromogranin B in an animal model of multiple sclerosis

Mo, Michelle; Hoang, Ha Thi; Schmidt, Stefan; Clark, Robert B.; Ehrlich, Barbara E.

doi:10.1016/j.mcn.2013.04.003

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…Increased levels of Sg1 could cause increased cytosolic calcium levels which further activates calcium dependent proteases, like calpain. These proteases can cleave the intracellular calcium channel 1,4,5‐trisphosphate receptor type I which results in a further increase of the cytosolic calcium levels .…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis

et al. 2015

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Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase-3-like protein 1, secretogranin-1 (Sg1), cerebellin-1, neuroserpin, cell surface glycoprotein MUC18, testican-2 and glutamate receptor 4. An independent sample set of 13 early-MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early-MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease.

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Section: Discussionmentioning

confidence: 99%

Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis

et al. 2015

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“…Lastly, ITPR3 is a protein in the endoplasmic reticulum (ER) membrane that increases the release of calcium from the ER to the cytoplasm of neurons. This triggers a downstream signaling cascade that can eventually result in neuronal death/neurodegeneration in both the EAE mouse model of MS [ 69 ] and stem cell-derived neurons from MS patients [ 70 ], as sustained high calcium levels in cells/neurons are highly toxic.…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing in Multi-Incident Families Identifies Novel Candidate Genes for Multiple Sclerosis

Horjus

Mourik-Banda

Heerings

et al. 2022

IJMS

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Multiple sclerosis (MS) is a degenerative disease of the central nervous system in which auto-immunity-induced demyelination occurs. MS is thought to be caused by a complex interplay of environmental and genetic risk factors. While most genetic studies have focused on identifying common genetic variants for MS through genome-wide association studies, the objective of the present study was to identify rare genetic variants contributing to MS susceptibility. We used whole exome sequencing (WES) followed by co-segregation analyses in nine multi-incident families with two to four affected individuals. WES was performed in 31 family members with and without MS. After applying a suite of selection criteria, co-segregation analyses for a number of rare variants selected from the WES results were performed, adding 24 family members. This approach resulted in 12 exonic rare variants that showed acceptable co-segregation with MS within the nine families, implicating the genes MBP, PLK1, MECP2, MTMR7, TOX3, CPT1A, SORCS1, TRIM66, ITPR3, TTC28, CACNA1F, and PRAM1. Of these, three genes (MBP, MECP2, and CPT1A) have been previously reported as carrying MS-related rare variants. Six additional genes (MTMR7, TOX3, SORCS1, ITPR3, TTC28, and PRAM1) have also been implicated in MS through common genetic variants. The proteins encoded by all twelve genes containing rare variants interact in a molecular framework that points to biological processes involved in (de-/re-)myelination and auto-immunity. Our approach provides clues to possible molecular mechanisms underlying MS that should be studied further in cellular and/or animal models.

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“…Lastly, ITPR3 is a protein in the endoplasmic reticulum (ER) membrane that increases the release of calcium from the ER to the cytoplasm of neurons. This triggers a downstream signaling cascade that can eventually result in neuronal death/neurodegeneration in both the EAE mouse model of MS 74 and stem cell-derived neurons from MS patients 75 , as sustained high calcium levels in cells/neurons are highly toxic.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing in multi-incident families identifies novel candidate genes for multiple sclerosis

Horjus

Banda

Heerings

et al. 2022

Preprint

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Multiple sclerosis (MS) is a degenerative disease of the central nervous system in which auto-immunity-induced demyelination occurs. MS is thought to be caused by a complex interplay of environmental and genetic risk factors. While most genetic studies have focused on identifying common genetic variants for MS through genome-wide association studies, the objective of the present study was to identify rare genetic variants contributing to MS susceptibility. We used whole exome sequencing (WES) followed by co-segregation analyses in nine multi-incident families with 2 to 4 affected individuals. WES was performed in 31 family members with and without MS. After applying a suite of selection criteria, co-segregation analyses for a number of rare variants selected from the WES results were performed, adding 24 family members. This approach resulted in 12 exonic rare variants that showed acceptable co-segregation with MS within the nine families, implicating the genes MBP, PLK1, MECP2, MTMR7, TOX3, CPT1A, SORCS1, TRIM66, ITPR3, TTC28, CACNA1F, and PRAM1. Of these, three genes (MBP, MECP2, and CPT1A) have been previously reported as carrying MS-related rare variants. Six additional genes (MTMR7, TOX3, SORCS1, ITPR3, TTC28, and PRAM1) have also been implicated in MS through common genetic variants. The proteins encoded by all twelve genes containing rare variants interact in a molecular framework that points to biological processes involved in (de-/re-)myelination and auto-immunity. Our approach provides clues to possible molecular mechanisms underlying MS that should be further studied in cellular and/or animal models.

show abstract

The role of chromogranin B in an animal model of multiple sclerosis

Cited by 8 publications

References 40 publications

Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis

Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis

Whole Exome Sequencing in Multi-Incident Families Identifies Novel Candidate Genes for Multiple Sclerosis

Whole exome sequencing in multi-incident families identifies novel candidate genes for multiple sclerosis

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