Nefh — Neurofilament Heavy Chain is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
NEFH (Neurofilament Heavy Chain) is a gene encoding the heavy subunit of the neuronal intermediate filament protein family. Neurofilaments are essential for maintaining axonal caliber and nerve conduction velocity. The NEFH gene is located on chromosome 22q12.1 and mutations cause Charcot-Marie-Tooth disease type 2 (CMT2) and are implicated in amyotrophic lateral sclerosis (ALS).
| NEFH — Neurofilament Heavy Chain | |
|---|---|
| Symbol | NEFH |
| Full Name | Neurofilament Heavy Chain |
| Chromosome | 22q12.1 |
| NCBI Gene | 4744 |
| Ensembl | ENSG00000100133 |
| OMIM | 162400 |
| UniProt | P06744 |
| Diseases | Amyotrophic Lateral Sclerosis, Charcot-Marie-Tooth Disease Type 2 |
| Expression | Large motor neurons, sensory neurons, brain (cortex, hippocampus, cerebellum) |
| Key Mutations | |
| E800K, S84F, R1652W, Q333X, 8008insC (polyglutamine expansion) | |
Neurofilament Heavy Chain (NF-H) is the largest neurofilament subunit (approximately 200 kDa) and plays critical roles in neuronal biology:
NEFH contains several distinctive features:
While NEFH mutations are not a common cause of ALS, they contribute to disease susceptibility and pathogenesis:
NEFH mutations cause an axonal (non-demyelinating) form of CMT:
Neurofilament proteins are affected in several other conditions:
NEFH expression is neuron-specific:
Julius N, et al. "Neurofilament heavy chain mutations cause Charcot-Marie-Tooth disease type 2." Brain 2012. DOI:10.1093/brain/aws222
Petzold A. "Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and disease." Brain 2005. DOI:10.1093/brain/awh269
Lu CH, et al. "Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis." Neurology 2012. DOI:10.1212/WNL.0b013e31825dceeb
Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are FDA-recognized biomarkers:
The study of Nefh — Neurofilament Heavy Chain has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Julien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998;61:1-23. DOI:10.1016/s0079-6603(0860826-4.
[2] Lee MK, Cleveland DW. Neuronal intermediate filaments: new progress on functions. Annu Rev Neurosci. 1996;19:187-217. DOI:10.1146/annurev.neuro.19.1.187
[3] Xu Z, Marszalek JR, Lee MK, et al. Subtle structural change in the NF-H tail domain caused by phosphorylation produces changes in its aggregation properties. J Biol Chem. 1998;273(42):27126-27134. DOI:10.1074/jbc.273.42.27126
[4] Lobsiger CS, Cleveland DW. Neurofilament phosphorylation and axonal degeneration: new insights into the complexity of region-specific pathology. Nat Rev Neurosci. 2002;3(10):777-784. DOI:10.1038/nrn933
[5] Perrot R, Eyer J. Neurofilament polymer integrity during axonal transport. J Neurochem. 2009;110(5):1504-1514. DOI:10.1111/j.1471-4159.2009.06280.x