Neurofilament light polypeptide

Neurofilament light polypeptide (NF-L) is a protein that in humans is encoded by the NEFL gene. Neurofilaments are type IV intermediate filaments found in the cytoplasm of neurons. They are a major component of the neuronal cytoskeleton and are involved in maintaining the structural integrity of neurons. NF-L, the light or low molecular weight polypeptide of the neurofilament triplet, plays a critical role in the assembly and maintenance of the neurofilament network.

Structure

Neurofilament light polypeptide is a protein with a molecular weight of approximately 68 kDa. It is the lightest component of the neurofilament triplet, which also includes medium (NF-M) and heavy (NF-H) polypeptides. NF-L has a central rod domain responsible for filament assembly, flanked by globular head and tail domains. The tail domain is involved in interactions with other cytoskeletal components and cellular organelles.

Function

NF-L is essential for the formation and maintenance of the neurofilament network within neurons. This network provides structural support for the neuron and is involved in the transport of molecules along the axon. NF-L interacts with the other neurofilament subunits (NF-M and NF-H) to form the neurofilament backbone, contributing to axonal diameter regulation and, consequently, to the conduction velocity of neuronal impulses.

Clinical Significance

Alterations in the expression or structure of NF-L can lead to neurodegenerative diseases. Elevated levels of NF-L in the cerebrospinal fluid (CSF) and blood have been associated with various neurological disorders, including Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Alzheimer's Disease. As such, NF-L is considered a potential biomarker for neurodegeneration and axonal damage.

Mutations in the NEFL gene can cause rare hereditary neuropathies, such as Charcot-Marie-Tooth Disease type 2E/1F. These mutations disrupt the normal assembly of neurofilaments, leading to axonal degeneration and the clinical manifestations of peripheral neuropathy.

Genetics

The NEFL gene is located on chromosome 8p21. It consists of multiple exons that encode the NF-L protein. Mutations in this gene, including point mutations and deletions, have been identified in patients with hereditary neuropathies.

Research Directions

Research on NF-L is focused on elucidating its role in the pathogenesis of neurodegenerative diseases and exploring its potential as a biomarker for early diagnosis and disease progression monitoring. Additionally, studies aim to understand the molecular mechanisms underlying the effects of NEFL mutations in hereditary neuropathies.

See Also

• Neurofilament
• Intermediate filament
• Neurodegenerative diseases
• Biomarker