Cofilin rod formation in neurons impairs neuronal structure and function.

Cofilin-1 is a major actin depolymerizer in the central nervous system. It is a member of the ADF/cofilin family that regulates the dynamics of actin filaments. The activity of cofilin-1 is regulated by the modulation of phosphorylation at its Ser3 residue, and its proper function is crucial for the structure and proper function of neurons. Cofilin rods, pathological structures composed of cofilin and actin, form under stress conditions. A high cofilin/F-actin ratio, cofilin dephosphorylation and/or cofilin oxidation are three major mechanisms of cofilin rod formation. Cofilin rods can be divided into cytoplasmic rods and nuclear rods. Cytoplasmic rods have been proved to disrupt dendritic transportation, cause synaptic loss and impair synaptic function, which maybe associated with neurodegenerative diseases such as Alzheimer's disease. On the other hand, the role of nuclear rods remains largely unknown. Further studies are needed to investigate the relationship and the underlying mechanisms of cofilin rod formation during the progression of various neurological diseases.