neurofilament

Neurofilaments are a class of intermediate filaments that form the cytoskeletal framework of neurons, especially abundant in axons where they contribute to axonal caliber and stability. They are heteropolymers of light, medium, and heavy subunits (NF-L, NF-M, NF-H), encoded by the NEFL, NEFM, and NEFH genes. In developing neurons alpha-internexin can substitute for a neurofilament subunit early in maturation; mature axons predominantly contain NF-L together with NF-M and NF-H. NF-H and NF-M carry long C-terminal tail domains rich in lysine-serine-proline (KSP) repeats that become extensively phosphorylated, a modification that governs filament spacing and axon diameter.

Function: Neurofilaments provide structural support along the axon and cooperate with microtubules and microfilaments to maintain axonal integrity and support long-range transport. The arrangement and phosphorylation state of NF-H and NF-M tails influence axon diameter, which in turn affects nerve conduction velocity. Dynamic turnover and reorganization of neurofilaments occur in response to neuronal activity and injury.

Clinical and research relevance: Abnormal neurofilament dynamics are linked to neurodegenerative and axonal disorders. Elevated levels of neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH) in CSF or blood are used as biomarkers of axonal injury and neurodegeneration in conditions such as ALS, multiple sclerosis, traumatic brain injury, and Alzheimer's disease. Mutations in NEFL, NEFM, or NEFH can cause inherited peripheral neuropathies and motor neuron diseases. Pathologically, neurofilament aggregates and inclusions may be observed in affected neurons in several diseases.

Histology and diagnostics: Neurofilaments are common targets for immunohistochemical staining to visualize neuronal processes in tissue sections and brain samples.