Center for Research in Neurobiology 'Daniel Bovet' (CRiN)

Wild-type TDP-43 forms cytosolic inclusions in patients afflicted by Amyotrophic Lateral Sclerosis (ALS). The origin of TDP-43 aggregates and the mechanisms used by cells to counteract TDP-43 aggregation are only partly understood. Stress conditions trigger the accumulation of TDP-43 in stress granules (SGs), which are dynamic RNA-containing condensates. The role of SGs in modulating TDP-43 aggregation is ambiguous. TDP-43 can misfold and aggregate independently of SGs, but chronic induction of SGs has been shown to trigger the formation of cytosolic TDP-43 inclusions that cause neurotoxicity. I will present data supporting the role of the protein quality control (PQC) and stress-induced post-translational modifications in preventing protein aggregation inside SGs. Potentiating the PQC of SGs could prevent TDP-43 aggregation during stress.