Modulating biomolecular condensates: a novel approach to drug discovery

DM Mitrea, M Mittasch, BF Gomes, IA Klein… - Nature Reviews Drug …, 2022 - nature.com
In the past decade, membraneless assemblies known as biomolecular condensates have
been reported to play key roles in many cellular functions by compartmentalizing specific …

Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis

SA Goutman, O Hardiman, A Al-Chalabi… - The Lancet …, 2022 - thelancet.com
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. The discovery of genes
associated with amyotrophic lateral sclerosis, commencing with SOD1 in 1993, started fairly …

Organ aging signatures in the plasma proteome track health and disease

HSH Oh, J Rutledge, D Nachun, R Pálovics, O Abiose… - Nature, 2023 - nature.com
Animal studies show aging varies between individuals as well as between organs within an
individual,,–, but whether this is true in humans and its effect on age-related diseases is …

TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A

AL Brown, OG Wilkins, MJ Keuss, SE Hill, M Zanovello… - Nature, 2022 - nature.com
Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic
lateral sclerosis and frontotemporal dementia,–, two related neurodegenerative diseases …

Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies

MW Baughn, Z Melamed, J López-Erauskin… - Science, 2023 - science.org
Loss of nuclear TDP-43 is a hallmark of neurodegeneration in TDP-43 proteinopathies,
including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 …

TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A

XR Ma, M Prudencio, Y Koike, SC Vatsavayai, G Kim… - Nature, 2022 - nature.com
A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral
sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein …

Mis-spliced transcripts generate de novo proteins in TDP-43–related ALS/FTD

S Seddighi, YA Qi, AL Brown, OG Wilkins… - Science translational …, 2024 - science.org
Functional loss of TDP-43, an RNA binding protein genetically and pathologically linked to
amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leads to the …

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS–FTD

KE Irwin, P Jasin, KE Braunstein, IR Sinha, MA Garret… - Nature medicine, 2024 - nature.com
Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well
documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal …

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 …

Stress granules and neurodegeneration

B Wolozin, P Ivanov - Nature Reviews Neuroscience, 2019 - nature.com
Recent advances suggest that the response of RNA metabolism to stress has an important
role in the pathophysiology of neurodegenerative diseases, particularly amyotrophic lateral …