A large body of literature suggests that amyotrophic lateral sclerosis (ALS) pathology is intimately linked with neuroinflammation, specifically activation and recruitment of microglia and astrocytes. The actual cause of gliosis is unclear. Extracellular Cu/Zn superoxide dismutase (SOD1) has recently been shown to activate microglia in a CD14 dependant mechanism providing one potential pathway by which glial cells become activated. As protein inclusions are thought to be an important part of ALS pathology and are associated with all forms of ALS, we sought to determine if aggregated SOD1 would activate microglia. Recombinant SOD1 was aggregated and this, or monomeric forms of SOD1 were then added to EOC.13 microglial cells or primary microglial cells in culture. Although monomeric mutant SOD1 has been shown to promote microglial activation in the past, we found that aggregated SOD1 was able to much more efficiently activate microglia in culture when compared with the unaggregated form of mutant SOD1. In addition to CD14 dependant pathways, aggregated SOD1 also bound to the surface of glial cells and was internalized in a lipid raft and scavenger receptor dependent manner. We have for the first time shown that aggregated mutant SOD1 potently activates microglia. These results suggest that there may be a potential link between protein aggregation and microglial activation in ALS.

Institutions are not necessarily good environments for children. In the face of challenges such as HIV, Ebola, poverty, conflict and disaster the numbers have grown rather than reduced. Some countries have closed institutions down -driven by findings that cognitive developmental delay is associated with institutional care. Yet insight into abuse and violence within institutionalised settings is neglected. Maltreatment -violence and abuse -may be an issue. This systematic review series addresses violence and abuse experiences in institutionalised care, exploring firstly the frequency of abuse/violence in institutions, secondly any interventions to reduce such violence or abuse and thirdly the perpetrators of such violence or abuse. The final systematic review updates the findings on cognitive delay associated with institutionalised care. With a violence lens, cognitive delay may well be considered under the umbrella of neglect. Maltreatment and abuse may be a driver of cognitive delay. The keyword search covered several electronic databases and studies were included for data abstraction if they met adequacy criteria. Eight studies were identified on the prevalence of abuse in institutions and a further three studies reported on interventions. Only one study was identified documenting peer on peer violence in institutions. Sixty-six studies were identified examining cognitive development for institutionalised children. All but two of these record cognitive deficits associated with institutionalisation. Only two asked about violence or abuse which was found to be higher in institutionalised children. Overall the abuse experiences of children in institutions are poorly recorded, and in one study violence was associated with high suicidal attempts. The major intervention pathway for ameliorating cognitive challenge seems to be placement out of the institutions which shows benefits and redresses some cognitive outcomes - yet not a total panacea. The single study providing training and monitoring of harsh punishment and maltreatment showed immediate and decided reductions. This data suggest, despite the paucity of studies, violence and abuse, by commission or omission is prevalent in institutions, has an effect on child well-being and is amenable to intervention. Simple training or more complex structures to place children within conducive alternative environments (or to avoid institutionalised placements in the first place) seem to be the main pathway of intervention.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease. The mechanism that underlies amyotrophic lateral sclerosis (ALS) pathology remains unclear, but protein inclusions are associated with all forms of the disease. Apart from pathogenic proteins, such as TDP-43 and SOD1, other proteins are associated with ALS inclusions including small heat shock proteins. However, whether small heat shock proteins have a direct effect on SOD1 aggregation remains unknown. In this study, we have examined the ability of small heat shock proteins αB-crystallin and Hsp27 to inhibit the aggregation of SOD1 in vitro. We show that these chaperone proteins suppress the increase in thioflavin T fluorescence associated with SOD1 aggregation, primarily through inhibiting aggregate growth, not the lag phase in which nuclei are formed. αB-crystallin forms high molecular mass complexes with SOD1 and binds directly to SOD1 aggregates. Our data are consistent with an overload of proteostasis systems being associated with pathology in ALS.