ALS genetics: gains, losses, and implications for future therapies

G Kim, O Gautier, E Tassoni-Tsuchida, XR Ma… - Neuron, 2020 - cell.com
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder caused by the loss
of motor neurons from the brain and spinal cord. The ALS community has made remarkable …

Genetics of amyotrophic lateral sclerosis: seeking therapeutic targets in the era of gene therapy

N Suzuki, A Nishiyama, H Warita, M Aoki - Journal of human genetics, 2023 - nature.com
Amyotrophic lateral sclerosis (ALS) is an intractable disease that causes respiratory failure
leading to mortality. The main locus of ALS is motor neurons. The success of antisense …

Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins

T Altman, A Ionescu, A Ibraheem, D Priesmann… - Nature …, 2021 - nature.com
Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in
motor neurons of~ 95% of amyotrophic lateral sclerosis (ALS) patients, but the contribution …

RNA transport and local translation in neurodevelopmental and neurodegenerative disease

MS Fernandopulle, J Lippincott-Schwartz… - Nature …, 2021 - nature.com
Neurons decentralize protein synthesis from the cell body to support the active metabolism
of remote dendritic and axonal compartments. The neuronal RNA transport apparatus …

Liquid-liquid phase separation of TDP-43 and FUS in physiology and pathology of neurodegenerative diseases

JL Carey, L Guo - Frontiers in molecular biosciences, 2022 - frontiersin.org
Liquid-liquid phase separation of RNA-binding proteins mediates the formation of numerous
membraneless organelles with essential cellular function. However, aberrant phase …

Disruption of RNA metabolism in neurological diseases and emerging therapeutic interventions

JK Nussbacher, R Tabet, GW Yeo, C Lagier-Tourenne - Neuron, 2019 - cell.com
RNA binding proteins are critical to the maintenance of the transcriptome via controlled
regulation of RNA processing and transport. Alterations of these proteins impact multiple …

Neuromuscular junction dysfunction in amyotrophic lateral sclerosis

S Verma, S Khurana, A Vats, B Sahu, NK Ganguly… - Molecular …, 2022 - Springer
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by
progressive degeneration of motor neurons leading to skeletal muscle denervation. Earlier …

Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions

JD Pereira, DM DuBreuil, AC Devlin, A Held… - Nature …, 2021 - nature.com
Human induced pluripotent stem cells (iPSC) hold promise for modeling diseases in
individual human genetic backgrounds and thus for develo** precision medicine. Here …

Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease

M Eshraghi, PP Karunadharma, J Blin… - Nature …, 2021 - nature.com
The polyglutamine expansion of huntingtin (mHTT) causes Huntington disease (HD) and
neurodegeneration, but the mechanisms remain unclear. Here, we found that mHtt promotes …

mRNA transport, translation, and decay in adult mammalian central nervous system axons

J Jung, J Ohk, H Kim, CE Holt, HJ Park, H Jung - Neuron, 2023 - cell.com
Localized mRNA translation regulates synapse function and axon maintenance, but how
compartment-specific mRNA repertoires are regulated is largely unknown. We developed an …