Neurofilaments

Neurofilaments are a major class of intermediate filaments that form part of the cytoskeleton of neurons, with a particular abundance in axons. They help give axons their structural integrity and influence their diameter, which in turn affects nerve conduction velocity. In vertebrates the core subunits are neurofilament light (NF-L), medium (NF-M), and heavy (NF-H). Alpha-internexin can form heteropolymers with NF-L and NF-M, and peripheral neurons may express additional intermediate filament proteins such as peripherin. Neurofilaments assemble from these subunits into 10-nanometer-diameter filaments that feature a central rod domain and long, largely unstructured tail domains, especially in NF-M and NF-H.

Functions of neurofilaments include providing mechanical support for long axons, contributing to axonal caliber, and organizing the axonal cytoskeleton to facilitate efficient transport of organelles and vesicles. They interact with microtubules, actin, and various motor and adaptor proteins to coordinate cytoskeletal dynamics and cargo movement along the axon. Post-translational modifications, notably phosphorylation of the tail domains of NF-H and NF-M, influence filament spacing, interactions with other cytoskeletal elements, and the rate of axonal transport, contributing to the maturation and maintenance of neurons.

In disease and clinical research, abnormal accumulation or disorganization of neurofilaments is observed in several neurodegenerative conditions. The light chain (NfL) is released into cerebrospinal fluid and blood following axonal injury, and its levels serve as a biomarker for neuronal damage and disease progression in disorders such as amyotrophic lateral sclerosis and other neurodegenerative diseases.

Genes encoding neurofilament proteins include NEFL (NF-L), NEFM (NF-M), and NEFH (NF-H). Mutations can disrupt filament assembly and axonal function, contributing to neuropathies.