ALS genetics, mechanisms, and therapeutics: where are we now?

R Mejzini, LL Flynn, IL Pitout, S Fletcher… - Frontiers in …, 2019 - frontiersin.org
The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift
as the number of genes associated with the disease risk and pathogenesis, and the cellular …

The molecular language of membraneless organelles

E Gomes, J Shorter - Journal of Biological Chemistry, 2019 - ASBMB
Eukaryotic cells organize their intracellular components into organelles that can be
membrane-bound or membraneless. A large number of membraneless organelles, including …

Molecular interactions underlying liquid− liquid phase separation of the FUS low-complexity domain

AC Murthy, GL Dignon, Y Kan, GH Zerze… - Nature structural & …, 2019 - nature.com
The low-complexity domain of the RNA-binding protein FUS (FUS LC) mediates liquid−
liquid phase separation (LLPS), but the interactions between the repetitive SYGQ-rich …

[HTML][HTML] Neurodegenerative disease: models, mechanisms, and a new hope

AD Gitler, P Dhillon, J Shorter - Disease models & …, 2017 - journals.biologists.com
Neurodegeneration is a feature of many debilitating, incurable diseases that are rapidly
rising in prevalence, such as Parkinson's disease. There is an urgent need to develop new …

Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains

L Guo, HJ Kim, H Wang, J Monaghan, F Freyermuth… - Cell, 2018 - cell.com
RNA-binding proteins (RBPs) with prion-like domains (PrLDs) phase transition to functional
liquids, which can mature into aberrant hydrogels composed of pathological fibrils that …

ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function

T Murakami, S Qamar, JQ Lin, GSK Schierle, E Rees… - Neuron, 2015 - cell.com
The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS
and FTD remain controversial. We propose a model in which low-complexity (LC) domains …

Paraspeckles: where long noncoding RNA meets phase separation

AH Fox, S Nakagawa, T Hirose, CS Bond - Trends in biochemical sciences, 2018 - cell.com
Long noncoding RNA (lncRNA) molecules are some of the newest and least understood
players in gene regulation. Hence, we need good model systems with well-defined RNA and …

RNA-binding proteins with prion-like domains in health and disease

AF Harrison, J Shorter - Biochemical Journal, 2017 - portlandpress.com
Approximately 70 human RNA-binding proteins (RBPs) contain a prion-like domain (PrLD).
PrLDs are low-complexity domains that possess a similar amino acid composition to prion …

FUS-dependent liquid–liquid phase separation is important for DNA repair initiation

BR Levone, SC Lenzken, M Antonaci, A Maiser… - Journal of Cell …, 2021 - rupress.org
RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA
damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair …

Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis

SC Ling, M Polymenidou, DW Cleveland - Neuron, 2013 - cell.com
Breakthrough discoveries identifying common genetic causes for amyotrophic lateral
sclerosis (ALS) and frontotemporal dementia (FTD) have transformed our view of these …