NEFL/A0375

NEFL, also known as A0375, is the 68 kDa light polypeptide that forms part of neurofilaments, which are involved in maintenance of neurite caliber.

NEFL, also known as A0375, is the 68 kDa light polypeptide that forms part of neurofilaments, which are involved in maintenance of neurite caliber. NEFL is encoded by a four exon gene on human chromosome 8p21 and is the most abundant of the neurofilament proteins. Interaction of NEFL with the N-methyl-D-aspartate (NMDA) receptor may result in reduction of the ubiquitination of the NR1 subunit of NMDA. In one line of mice, targeted homozygous knock-out of the first exon led to abnormal axon morphology. Intermediate filament structures were present in neonates, but reduced in adults. Axon diameter was reduced, and the number of regenerating neurons reduced/delayed after facial or sciatic nerve crush. Defects in NEFL cause Charcot-Marie-Tooth disease type 1F (CMT1F), resulting in demyelination of peripheral neurons, with corresponding reduction in action potential conduction velocity. Onset of CMT1F is in early childhood. NEFL mutations also cause Charcot-Marie-Tooth disease type 2E, which involves progressive muscle weakness and atrophy.