Neurofilaments are essential structural proteins that form a major component of the cytoskeleton of neurons. They are composed of three light chains (NFL, NF-M, and NF-H) and play an important role in axonal architecture and transport. In addition, their expression is altered in a variety of neurological diseases, including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. In this article, we review the structure, function, and regulation of neurofilaments, and discuss the potential roles of these proteins in neurodegenerative diseases.
Neurofilaments are intermediate filaments that form the core of the neuronal cytoskeleton. They are composed of three light chains (NFL, NF-M, and NF-H) and are encoded by the genes NEFH, NEFL, and NEFM. The NFL and NF-M subunits form heterodimers, which in turn interact with the NF-H subunit to form the final filament. The NFL and NF-M subunits are expressed primarily in mature neurons, while the NF-H subunit is expressed in both neurons and glial cells. Neurofilaments are larger than other intermediate filaments, with a diameter of 10 nm, and are the most abundant cytoskeletal proteins in the axon.
Neurofilaments are critical for the proper architecture and function of the neuron. They provide structural support to the axon and help determine its diameter, conduction velocity, and branching pattern. Neurofilaments are also important for axonal transport, as they provide a scaffold for the movement of organelles and other molecules along the axon. In addition, neurofilaments participate in signal transduction by binding to cell surface receptors and other signaling molecules.
The expression of neurofilaments is tightly regulated during development and in response to various stimuli. Neurofilaments are upregulated in response to neuronal injury, suggesting that they may play a role in the recovery from injury. In addition, the expression of neurofilaments is altered in a variety of neurological diseases, including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis.
In conclusion, neurofilaments are essential structural proteins that form a major component of the neuronal cytoskeleton. They are involved in axonal architecture, axonal transport, and signal transduction, and their expression is altered in a variety of neurological diseases. Future studies will be necessary to elucidate the exact roles of neurofilaments in health and disease.
References
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Ebrahimi-Fakhari, D., & Cleveland, D. W. (2015). Neurofilaments in axonal maintenance and disease. Neuron, 86(3), 513-529.
Takahashi, S., & Takeuchi, H. (2010). Regulation of Neurofilament Expression in Neurons. Molecular Neurobiology, 42(2), 214-224.