NEFL

Fig1. Overview of the structure of neurofilaments and neurofilament light chain. (Lorenzo Gaetani, 2019)

What is NEFL Protein?

NEFL gene (neurofilament light chain) is a protein coding gene which situated on the long arm of chromosome 8 at locus 8p21. Together with the medium chain (NF-M) and heavy chain (NF-H), NEFL forms heterogeneous polymers that are essential for maintaining the structural integrity of neurons, especially axons. The proteins encoded by the NEFL gene contain α-helically coiled rod-like domains, as well as amino-terminal head and carboxy-terminal tail domains, which vary widely in length. Abnormal aggregation of NEFL is a pathological feature of certain neurological diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, etc. The NEFL protein is consisted of 543 amino acids and NEFL molecular weight is approximately 61.5 kDa.

What is the Function of NEFL Protein?

The NEFL protein, also known as the Neurofilament light chain (NF-L), is an important part of the intermediate filaments (IFs) that make up the cytoskeleton of neurons. Its functions are mainly involved in maintaining the morphological and mechanical stability of axons, regulating axon diameter and synaptic activity, and participating in the transport of organelles along axons. In addition, abnormal aggregation of NEFL has been associated with a variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), giant axonal neuropathy (GAN), and spinal muscular atrophy. In these diseases, mutated or abnormal NEFL accumulation may lead to neurological dysfunction.

NEFL Related Signaling Pathway

The NEFL signaling pathway is involved in regulating the growth and development of neurons. NEFL is a neuronal intermediate filament protein that plays a critical role in maintaining the integrity of the neuronal cytoskeleton. When NEFL is expressed in the brain, it interacts with other proteins to form a complex that regulates the activity of various signaling pathways. This complex includes the mitogen-activated protein kinase (MAPK) pathway, the Wnt/β-catenin pathway, and the Notch pathway. The MAPK pathway is involved in regulating cell proliferation, differentiation, and survival. The Wnt/β-catenin pathway is involved in regulating cell adhesion and polarity. The Notch pathway is involved in regulating cell fate decisions.

NEFL Related Diseases

NEFL proteins have been implicated in a variety of neurological disorders, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. As an indicator of disease activity in multiple sclerosis; As a biomarker of injury severity in HIV-associated nerve injury, brain injury and spinal cord injury; Affects the invasion and migration of tumor cells in certain types of cancer such as esophageal squamous cell carcinoma; It also plays a role in neurodevelopment, axon regeneration and hereditary anterior temporal degenerative diseases. Abnormal changes in NEFL levels can be used as biomarkers to diagnose and monitor these diseases.

Bioapplications of NEFL

NEFL-related applications are mainly related to the diagnosis and research of diseases in the field of neurology. As the main intermediate filament protein in neurons, the level change of NEFL can reflect the degree of damage of nerve tissue, therefore, by monitoring the level of NEFL, it can be used to assess the activity of a variety of acute and chronic neurological diseases such as neurodegenerative diseases, monitor treatment response, and serve as a biomarker to predict the prognosis of disease. In addition, antibodies against NEFL are widely used in various scientific studies, such as immunohistochemistry, ELISA, western blotting and other experimental techniques, to detect and locate the expression of NEFL in human and animal samples.