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 role of TDP-43 mislocalization in amyotrophic lateral sclerosis

TR Suk, MWC Rousseaux - Molecular neurodegeneration, 2020 - Springer
Since its discovery as a primary component in cytoplasmic aggregates in post-mortem tissue
of patients with Amyotrophic Lateral Sclerosis (ALS), TAR DNA Binding Protein 43 kDa (TDP …

The pathobiology of TDP-43 C-terminal fragments in ALS and FTLD

BA Berning, AK Walker - Frontiers in neuroscience, 2019 - frontiersin.org
During neurodegenerative disease, the multifunctional RNA-binding protein TDP-43
undergoes a vast array of post-translational modifications, including phosphorylation …

ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair

JR Klim, LA Williams, F Limone… - Nature …, 2019 - nature.com
The findings that amyotrophic lateral sclerosis (ALS) patients almost universally display
pathological mislocalization of the RNA-binding protein TDP-43 and that mutations in its …

Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis

K Oiwa, S Watanabe, K Onodera, Y Iguchi… - Science …, 2023 - science.org
The cytoplasmic aggregation of TAR DNA binding protein-43 (TDP-43), also known as TDP-
43 pathology, is the pathological hallmark of amyotrophic lateral sclerosis (ALS). However …

PIKFYVE inhibition mitigates disease in models of diverse forms of ALS

ST Hung, GR Linares, WH Chang, Y Eoh, G Krishnan… - Cell, 2023 - cell.com
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results from
many diverse genetic causes. Although therapeutics specifically targeting known causal …

Autophagy and ALS: mechanistic insights and therapeutic implications

JP Chua, H De Calbiac, E Kabashi, SJ Barmada - Autophagy, 2022 - Taylor & Francis
Mechanisms of protein homeostasis are crucial for overseeing the clearance of misfolded
and toxic proteins over the lifetime of an organism, thereby ensuring the health of neurons …

[HTML][HTML] Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations

NH Alami, RB Smith, MA Carrasco, LA Williams… - Neuron, 2014 - cell.com
The RNA-binding protein TDP-43 regulates RNA metabolism at multiple levels, including
transcription, RNA splicing, and mRNA stability. TDP-43 is a major component of the …

Protein aggregation in amyotrophic lateral sclerosis

AM Blokhuis, EJN Groen, M Koppers… - Acta …, 2013 - Springer
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the
aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have …

[HTML][HTML] TDP-43 proteinopathy and ALS: insights into disease mechanisms and therapeutic targets

EL Scotter, HJ Chen, CE Shaw - Neurotherapeutics, 2015 - Elsevier
Therapeutic options for patients with amyotrophic lateral sclerosis (ALS) are currently
limited. However, recent studies show that almost all cases of ALS, as well as tau-negative …