Neurofilaments: From Neuronal Cytoskeletal Scaffolds to Neurological Disease Biomarkers

The cytoskeleton consists of three types of cytosolic fibers: actin microfilaments, intermediate filaments, and microtubules. Neurofilaments are the major intermediate filaments found in neurons and consist of light (NFL), medium (NFM), and heavy (NFH) subunits. Similar in structure to other intermediate filament proteins, neurofilaments have a globular amino-terminal head, a central α-helical rod domain, and a carboxy-terminal tail. A heterotetrameric unit (NFL-NFM and NFL-NFH) forms a protofilament, with eight protofilaments comprising the typical 10 nm intermediate filament. While neurofilaments are critical for radial axon growth and determine axon caliber, microtubules are involved in axon elongation. PKA phosphorylates the head domain of NFL and NFM to inhibit neurofilament assembly. Research studies have shown neurofilament accumulations in many human neurological disorders, including Parkinson's disease (in Lewy bodies along with α-synuclein), Alzheimer's disease, Charcot-Marie-Tooth disease, and Amyotrophic Lateral Sclerosis (ALS).

Nestin is an intermediate filament family member protein that is structurally related to the neurofilament proteins. Globular tubulin subunits comprise the microtubule building block, with α/β-tubulin heterodimers forming the tubulin subunit common to all eukaryotic cells). High CNPase expression is seen in oligodendrocytes and Schwann cells as CNPase accounts for roughly 4% of the total myelin protein in the central nervous system. CNPase binds to tubulin heterodimers and plays a role in tubulin polymerization and oligodendrocyte process outgrowth . GFAP filaments are characteristic of differentiated and mature brain astrocytes. Thus, GFAP is commonly used by investigators as a marker for intracranial and intraspinal tumors arising from astrocytes.

Doublecortin is a microtubule associated protein that stabilizes and bundles microtubules. Doublecortin is expressed in neuronal precursor cells and expression is downregulated as neurons mature . Neuronal nuclei (NeuN, Fox-3, RBFOX3) is a nuclear protein expressed in most post-mitotic neurons of the central and peripheral nervous systems. NeuN is not detected in Purkinje cells, sympathetic ganglion cells, Cajal-Retzius cells, INL retinal cells, inferior olivary, or dentate nucleus neurons. As Doublecortin is downregulated, NeuN is upregulated. GFAP filaments are characteristic of differentiated and mature brain astrocytes. In addition, GFAP is commonly used by investigators as a marker for intracranial and intraspinal tumors arising from astrocytes. Myelin basic protein (MBP) is an abundant central nervous system (CNS) myelin membrane protein that plays an important role in nerve myelination. Myelin sheaths are multi-layered membranes derived from oligodendrocytes. Ki-67 is universally expressed among proliferating cells and absent in quiescent cells. Specifically, it is detected in proliferating cells in G1, S, G2, and mitosis, but not in the G0 resting phase.

Neurofilament from neuronal scaffold to biomarker in cerebrospinal fluid and peripheral blood.

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Flora Flora is a technical support expert at EnkiLife, familiar with immunology and neuroscience, dedicated to providing customers with high-quality product combinations and technical support to help achieve research in neurodegenerative diseases and other neuroscience areas.