Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In addition, other kinds of proteins include antibodies that protect an organism from infection, and hormones that send important signals throughout the body.
Internexin, alpha-internexin, is a Class IV intermediate filament approximately 66 KDa. The protein was originally purified from rat optic nerve and spinal cord. The protein copurifies with other neurofilament subunits, as it was originally discovered, however in some mature neurons it can be the only neurofilament expressed. The protein is present in developing neuroblasts and in the central nervous system of adults. The protein is a major component of the intermediate filament network in small interneurons and cerebellar granule cells, where it is present in the parallel fibers.
Peripherin is a type III intermediate filament protein expressed mainly in neurons of the peripheral nervous system. It is also found in neurons of the central nervous system that have projections toward peripheral structures, such as spinal motor neurons. Its size, structure, and sequence/location of protein motifs is similar to other type III intermediate filament proteins such as desmin, vimentin and glial fibrillary acidic protein. Like these proteins, peripherin can self-assemble to form homopolymeric filamentous networks, but it can also heteropolymerize with neurofilaments in several neuronal types. This protein in humans is encoded by the PRPH gene. Peripherin is thought to play a role in neurite elongation during development and axonal regeneration after injury, but its exact function is unknown. It is also associated with some of the major neuropathologies that characterize amyotropic lateral sclerosis (ALS), but despite extensive research into how neurofilaments and peripherin contribute to ALS, their role in this disease is still unidentified.
Neurofilaments (NF) are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules (~25 nm) and microfilaments (7 nm), they form the neuronal cytoskeleton. They are believed to function primarily to provide structural support for axons and to regulate axon diameter, which influences nerve conduction velocity. The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types based on their gene organization and protein structure. Types I and II are the keratins which are expressed in epithelia. Type III contains the proteins vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP). Type IV consists of the neurofilament proteins NF-L, NF-M, NF-H and α-internexin. Type V consists of the nuclear lamins, and type VI consists of the protein nestin. The type IV intermediate filament genes all share two unique introns not found in other intermediate filament gene sequences, suggesting a common evolutionary origin from one primitive type IV gene.
Aptamers are short sequences of artificial DNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities, with variable levels of off-target binding and are sometimes classified as chemical antibodies. Aptamers and antibodies can be used in many of the same applications, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes.
An antibody microarray is a specific form of protein microarray. In this technology, a collection of captured antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected. Antibody microarrays are often used for detecting protein expression from various biofluids including serum, plasma and cell or tissue lysates. Antibody arrays may be used for both basic research and medical and diagnostic applications.
Thy-1 or CD90 is a 25–37 kDa heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antigen. Thy-1 can be used as a marker for a variety of stem cells and for the axonal processes of mature neurons. Structural study of Thy-1 led to the foundation of the Immunoglobulin superfamily, of which it is the smallest member, and led to some of the initial biochemical description and characterization of a vertebrate GPI anchor and also the first demonstration of tissue specific differential glycosylation.
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.
High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.
TAR DNA-binding protein 43 is a protein that in humans is encoded by the TARDBP gene.
Neurofilament medium polypeptide (NF-M) is a protein that in humans is encoded by the NEFM gene.
C-jun-amino-terminal kinase-interacting protein 4 is a scaffold protein that in humans is encoded by the SPAG9 gene.
Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.
Gigaxonin also known as kelch-like protein 16 is a protein that in humans is encoded by the GAN gene.
Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. It is mostly expressed in the thymus, spleen and white blood cells. The Gene for DR6 is 78,450 bases long and is found on the 6th chromosome. This is transcribed into a 655 amino acid chain weighing 71.8 kDa. Post transcriptional modifications of this protein include glycosylation on the asparagines at the 82, 141, 252, 257, 278, and 289 amino acid locations.
Neurofilament light polypeptide, also known as neurofilament light chain, abbreviated to NF-L or Nfl and with the HGNC name NEFL is a member of the intermediate filament protein family. This protein family consists of over 50 human proteins divided into 5 major classes, the Class I and II keratins, Class III vimentin, GFAP, desmin and the others, the Class IV neurofilaments and the Class V nuclear lamins. There are four major neurofilament subunits, NF-L, NF-M, NF-H and α-internexin. These form heteropolymers which assemble to produce 10nm neurofilaments which are only expressed in neurons where they are major structural proteins, particularly concentrated in large projection axons. Axons are particularly sensitive to mechanical and metabolic compromise and as a result axonal degeneration is a significant problem in many neurological disorders. The detection of neurofilament subunits in CSF and blood has therefore become widely used as a biomarker of ongoing axonal compromise. The NF-L protein is encoded by the NEFL gene. Neurofilament light chain is a biomarker that can be measured with immunoassays in cerebrospinal fluid and plasma and reflects axonal damage in a wide variety of neurological disorders. It is a useful marker for disease monitoring in amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and more recently Huntington's disease. It is also promising marker for follow-up of patients with brain tumors. Higher levels of blood or CSF NF-L have been associated with increased mortality, as would be expected as release of this protein reflects ongoing axonal loss. Recent work performed as a collaboration between EnCor Biotechnology Inc. and the University of Florida showed that the NF-L antibodies employed in the most widely used NF-L assays are specific for cleaved forms of NF-L generated by proteolysis induced by cell death. Methods used in different studies for NfL measurement are sandwich enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence, and high-sensitive single molecule array (SIMOA).
Affimer molecules are small proteins that bind to target proteins with affinity in the nanomolar range. These engineered non-antibody binding proteins are designed to mimic the molecular recognition characteristics of monoclonal antibodies in different applications. These affinity reagents have been optimized to increase their stability, make them tolerant to a range of temperatures and pH, reduce their size, and to increase their expression in E.coli and mammalian cells.
Several biomarkers for diagnosis of multiple sclerosis, disease evolution and response to medication are under research. While most of them are still under research, there are some of them already well stablished:
Mathias Jucker is a Swiss neuroscientist, Professor, and a Director at the Hertie Institute for Clinical Brain Research of the University of Tübingen. He is also a group leader at the German Center for Neurodegenerative Diseases in Tübingen. Jucker is known for his research on the basic biologic mechanisms underlying brain aging and Alzheimer’s disease.
Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the SARM1 gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzymatic activity that is highly conserved from archaea, plants, nematode worms, fruit flies, and humans. In mammals, SARM1 is highly expressed in neurons, where it resides in both cell bodies and axons, and can be associated with mitochondria.
