Protein aggregation diseases: pathogenicity and therapeutic perspectives

By A. Aguzzi, Tracy O'Connor. Nature reviews. Drug discovery, 2010

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Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes (2011, background): “BACE1 knockout did not have an overt effect on the mouse phenotype unlike γ-secretase inhibitio”
Phosphorylation of the FUS low‐complexity domain disrupts phase separation, aggregation, and toxicity (2017, positive): “Protein aggregation is a common hallmark of neurodegenerative disease (Harper & Lansbury, 1997; Trojanowski et al , 1998; Koo et al , 1999; Aguzzi & O’Connor, 2010) although the mechanisms of toxicity remain poorly understood.”
Mutations in UBQLN2 cause dominant X-linked juvenile and adult onset ALS and ALS/dementia (2011, neutral): “Although an impaired UPS is thought to be associated with the formation of proteinaceous inclusions in many neurodegenerative disorders, direct evidence of mutations in the UPS pathway has been limited 30 .”