Fig. 1.

Neurofilament Structure and Degeneration in Neurons and Astrocytes. In neurons, neurofilaments (NfL, NfM, NfH, α-internexin, peripherin) are crucial for maintaining structure and function. In astrocytes, GFAP, with its head, rod, and tail domains essential for structural integrity, plays a similar role. Neurofilament subunits are depicted with conserved α-helical rod domains and variable head and tail domains, showing phosphorylation and O-linked glycosylation, especially in the tails of NfM and NfH. Neurofilament assembly begins with monomers forming coiled-coil heterodimers, which align into tetramers and then assemble into mature filaments (∼10 nm in diameter). GFAP in astrocytes similarly contributes to cellular structure with its distinct domains. Upon axonal and astrocytic damage, neurofilament and GFAP proteins are released into the extracellular space, cerebrospinal fluid (CSF), and blood. These cleavage products can be detected by highly sensitive immunoassays, making them valuable biomarkers for diagnosing neurological disorders.