Chronic non-cancer pain in children: we have a problem, but also solutions.

Chronic non-cancer pain in children and adolescents has been described as "a modern public health disaster" that has generated significant medical and economic burdens within society. Seen as a disease in its own right, chronic pain has short and long-term consequences that impact not only the patient's health but also that of friends and families, due to significant parenting stress and disruptions in family life and structure. The evidence supporting pharmacological treatments and interventional procedures is limited, and no single strategy has been shown to be completely effective in children with chronic non-cancer pain.

TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis.

See Fratta and Isaacs (doi:10.1093/brain/awy091) for a scientific commentary on this article.The RNA binding proteins TDP-43 (encoded by TARDBP) and hnRNP A1 (HNRNPA1) are each mutated in certain amyotrophic lateral sclerosis cases and are often mislocalized in cytoplasmic aggregates within motor neurons of affected patients.

Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, a cell type that is intrinsically more vulnerable than other cell types to exogenous stress. The interplay between genetic susceptibility and environmental exposures to toxins has long been thought to be relevant to ALS. One cellular mechanism to overcome stress is the formation of small dense cytoplasmic domains called stress granules (SG) which contain translationally arrested mRNAs.