Neurofilament light polypeptide

Neurofilament light polypeptide (NF-L) is a structural protein encoded by NEFL that serves as a core component of neuronal intermediate filaments. It functions alongside neurofilament medium and heavy chains to maintain neuronal caliber and support the formation of neuronal filamentous networks (UniProt: P07196).

NF-L is expressed throughout the nervous system and is involved in maintaining neuronal structure and integrity. UniProt associates NEFL mutations with peripheral neuropathies, including Charcot-Marie-Tooth disease types CMT1F, CMT2E, and CMTDIG, which involve progressive weakness and axonal degeneration.

In Alzheimer's disease, NF-L is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.1976; Chaparral AD proteomics). This reduction was measured across subcellular fractions using quantitative proteomics in human post-mortem brain tissue. The downregulation of this structural protein in AD brain may reflect neuronal loss or cytoskeletal disruption associated with neurodegeneration in Alzheimer's disease.