Nefl-KO Mouse

NEFL, encoding the neurofilament light chain protein, is a neuronal cytoplasmic protein highly expressed in large calibre myelinated axons. It plays a crucial role in maintaining axonal integrity and function. Its levels in cerebrospinal fluid (CSF) and blood increase proportionally to the degree of axonal damage in various neurological disorders, making it a promising biomarker [1].

Pathogenic variants in NEFL cause different forms of Charcot-Marie-Tooth disease (CMT), including demyelinating, axonal and intermediate forms, with varying severity [3]. In a Taiwanese CMT cohort, NEFL mutations accounted for 1.8% of CMT patients, and some patients had additional central nervous system (CNS) involvement [4]. In two Italian families, CMT related to a specific NEFL mutation was associated with a mild, childhood-onset phenotype, along with new findings of cardiological and urinary dysfunctions [5].

In esophageal squamous carcinoma cells, NEFL overexpression promotes invasion and migration via the EGFR/AKT/S6 pathway [2]. Also, in breast cancer, NEFL mRNA level is a potential prognostic factor for early-stage patients, being down-regulated in lymph node metastases compared to primary tumors [6].

In children and adolescents with schizophrenia and bipolar disorder, serum NEFL levels are increased, indicating neuronal damage [7].

In conclusion, NEFL is essential for axonal function and its abnormal variants or expression are associated with multiple neurological and some non-neurological diseases. Studies on NEFL-related phenotypes and diseases contribute to understanding disease mechanisms and potentially developing new diagnostic and therapeutic strategies.