E. Onesto

TL;DR: Using motor neuronal fALS models, it is demonstrated that HspB8 decreases aggregation and increases mutant SOD1 solubility and clearance, without affecting wild-type S OD1 turnover, and the pharmacological modulation of HSpB8 expression in motor neurons may have important implications to unravel the molecular mechanisms involved both in fALS and in sALS.

TL;DR: The RNA-binding proteins TDP-43 and FUS form abnormal cytoplasmic aggregates in affected tissues of patients with amyotrophic lateral sclerosis and frontotemporal lobar dementia as discussed by the authors.

TL;DR: The toxicity of mutant SOD1 might, therefore, arise from an initial misfolding reducing nuclear protection from the active enzyme (loss of function in the nuclei), a process that may be involved in ALS pathogenesis.

TL;DR: It is speculated that TARDBP and C9ORF72 mutations might trigger cell death by impairing not only RNA metabolism, but also mitochondria activity in ALS/FTD neurons.

TL;DR: How the PolyGln neurotoxicity of SBMA AR may be either mediated or decreased by aggregates is discussed, and data on the dual role played by testosterone on motor neuronal functions and dysfunctions is presented.