Abstract
Dysregulation of iron metabolism and aberrant iron deposition has been associated with multiple sclerosis. However, the factors that contribute to this pathological state remain to be understood. In this study, human multiple sclerosis and mice brain samples were analyzed through mass spectrometry as well as histological and immunoblot techniques, which demonstrated that iron deposition is associated with increased levels of nuclear prelamin A recognition factor (NARF). NARF is a protein associated with the mitochondria which has also been linked to mitochondrial defects in multiple sclerosis. We report NARF to be associated in multiple sclerosis pathology and aberrant iron deposition.
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Acknowledgements
This work was supported by an unrestricted grant to the University of Miami from Research to Prevent Blindness (RPB), Department of Defense grant WHX81-16-0715 and NIH grant EY14801.
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The study protocol was approved by the University of Miami Institutional Review Board, and the use of human pathological samples is in compliance with the National Institute of Health Code E4. Animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Miami and guidelines for the euthanasia of animals were in compliance with the American Veterinary Medical Association (AVMA).
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Fig. S1
No detectable changes in expression of NARF based on the data from NCBI GEO repository [accession numbers: GDS3920, GDS3886 (blood); GDS2978, GDS4218 (brain); GDS4150 (T cells)]. a Gene expression comparison of multiple sclerosis and the controls. b NARF mRNA expression between human and mouse brain samples (PNG 331 kb)
Fig. S2
Summary of Pathology Report for Multiple Sclerosis Tissue. Images provided by the Human Brain and Spinal Fluid Resource Center for the neuronal regions which samples were collected from (PNG 2892 kb)
Fig. S3
Summary of Pathology Report for Normal Tissue. Images provided by the Human Brain and Spinal Fluid Resource Center for the neuronal regions which samples were collected from (PNG 3014 kb)
Online Resource 1
Detailed Pathology Report for Multiple Sclerosis Tissue. Neuropathology report from the Human Brain and Spinal Fluid Resource Center, Los Angeles, CA (PDF 428 kb)
Online Resource 2
Detailed Pathology Report for Normal Tissue. Neuropathology report from the Human Brain and Spinal Fluid Resource Center, Los Angeles, CA (PDF 428 kb)
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Ding, D., Valdivia, A.O. & Bhattacharya, S.K. Nuclear prelamin a recognition factor and iron dysregulation in multiple sclerosis. Metab Brain Dis 35, 275–282 (2020). https://doi.org/10.1007/s11011-019-00515-z
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DOI: https://doi.org/10.1007/s11011-019-00515-z