Ongoing Studies of Deimination in Neurodegenerative Diseases Using the F95 Antibody
Over the past decade, growing evidence has emerged, suggesting that protein deimination is increased in human neurodegenerative disorders such as Alzheimer's disease, Creutzfeldt–Jakob disease, and Parkinson's disease. As an additional tool to identify affected proteins, some of these experiments utilized the F95 monoclonal antibody, which can theoretically recognize any protein in which arginine amino acids have been transformed to citrullines. This chapter outlines previous studies of brain protein deimination in these aforementioned maladies using F95 as well as ongoing unpublished studies of other neurodegenerative disorders such as Alexander's disease, amyotrophic lateral sclerosis, diffuse Lewy body disease, some primary astrocytic neoplasms, and normal brain aging. In addition, some data associated with the animal models of these conditions are also presented. Collectively, most of these conditions support the trending concept that neurodegeneration, for whatever reason, is accompanied by amplified citrullination, although the proteins affected and pattern of increased deimination in the central nervous system may differ in different disease states.
KeywordsAging Alexander disease Alzheimer’s disease Amyotrophic lateral sclerosis Creutzfeldt–Jakob disease Diffuse Lewy body disease Glioma Parkinson’s disease
These experiments were supported by the Research Program of the Department of Veterans Health Administration and grants from the Parkinson Association of Alabama, The Strain Family Foundation, and an MREP Award from the Department of Veterans Affairs. MB and MH were supported by NIH grant P01NS42803. We also would like to thank Deborah Freemen, Joshua D. Echols, Jeffery L. King, Kiran B. Gupta, Carey McInnis, William W. Snow, Sapan Majmundar, Padmapriya Vattem, Dr. Thiagarajan Sambandam, and Dr. Christopher C. Gelwix for technical assistance.
In addition, we also gratefully acknowledge the numerous sources of human brain specimens, including Dr. Francine M Benes of the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number MH/NS 31862; Dr. H. Ronald Zielke of the Brain and Tissue Bank for Developmental Disorders at the University of Maryland in Baltimore; Dr. William W. Tourtellotte of the National Neurological Research Specimen Bank, VAMC, in Los Angeles, which is sponsored by NINDS/NIMH, National Multiple Sclerosis Society, VA Greater Los Angeles Healthcare System, and Veterans Health Services and Research Administration, Department of Veterans Affairs; and Drs. Steven Carroll and Richard Powers of the Alzheimer’s Disease Research Center Neuropathology Core and the Brain Resource Program at the University of Alabama at Birmingham, which were sponsored in part by National Institutes of Health, grant numbers P50 AG016582, NP30 NS57098, and P30 NS47466. Finally, we would also like to specifically thank Dr. Yancey Gillespie, for providing human astrocytic tumor specimens, and the Pathology Department of the University of Alabama at Birmingham, for glioma samples and spinal cords from ALS and control patients.
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