FIGURE 2.

Cofilin-actin rod causes and effects. Cytoplasmic rods can be induced by multiple types of stress, such as ATP depletion, oxidative stress, and a decrease in cellular pH. Dephosphorylation of cofilin and association with actin in a 1:1 ratio leads to rod formation in the presence of oxidative stress. Post-translational modifications (PTM) of actin and cofilin may also be an emerging area for rod regulation. The rods block critical intracellular trafficking of organelles such as mitochondria and results in ATP depletion and impaired synaptic activity. The disruption of actin dynamics due to sequestered cofilin decreases dendritic spines and loss of synaptic plasticity, leading to loss of memory and cognitive ability over time. Interestingly, nuclear rods are similarly formed in the nucleus after nuclear translocation due to heat shock, DMSO, or ATP depletion. Other actin-binding proteins (ABPs), including the Huntingtin mutant, associate with the nuclear rods and form persistent rods that can affect transcription and chromatin remodeling. Both cytoplasmic and nuclear rods can lead to AD, HD, and PD pathologies.