Mislocalization and aggregation of the RNA-binding proteins (RBPs) FUS and TDP-43 are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), contributing to c...

Phosphorothioates, stereospecific modifications of the RNA phosphate backbone in anaerobic archaea, expand the epitranscriptome beyond nucleobases and ribose sugars. Installed by Esti enzymes at conse...

Dinnyés and colleagues reviewed past and current developments in safety and toxicity assessment of antisense oligonucleotides affecting the central nervous system. They provided insights into how thei...

Poly(ADP-ribose) (PAR) is an RNA-like polymer that regulates an increasing number of biological processes. Dysregulation of PAR is implicated in neurodegenerati

Cells use multiple protein quality control (PQC) mechanisms to counteract the toxic effects of protein aggregation caused by cellular stress, ageing or disease. While it is known that PQC mechanisms d...

Nature Aging - Gao et al. identify a toxicity-driving region within TDP-43 and show that a brain-penetrant small molecule targeting this region improves mitochondrial function, reduces...

BACKGROUND TAR DNA binding protein - 43 (TDP-43) nuclear loss is a pathological hallmark of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and related neurodegenerative disorders....

The sequence-encoded determinants underlying aberrant sTDP-43 behavior are defined, revealing therapeutic strategies for ALS.

Longitudinal multi-omics in SOD1-ALS mice identifies a disease-associated motor neuron (DM) state transition driven by transcription factor networks. Features of this state are conserved in human ALS ...

The cytoplasm of vertebrate cells is compartmentalized into the cytosol and several messenger RNA (mRNA)-scaffolded condensates, present at steady-state conditions and in the absence of stress. They i...

Pathological tau aggregates drive neuronal dysfunction in Alzheimer’s disease (AD) and related tauopathies, yet no approved therapy eliminates existing tau neurofibrillary tangles. Here, we report the...

Cytosolic inclusions of the RNA-binding protein TDP-43 are a pathological hallmark of several neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Cellular or...

Pathological protein misfolding and aggregation underlie many devastating human diseases, yet strategies to selectively neutralize aggregation-prone protein states without perturbing their normal func...

Highly conserved mRNA 3′ UTRs act as co-translational chaperones for intrinsically disordered regions (IDRs), preventing inter-domain misfolding and enabling biogenesis of fully active proteins.

Ryan et al. have developed a high-throughput approach for identifying variants of the amyloid disaggregase Hsp104. Their approach facilitates analysis of large Hsp104 variant libraries in parallel and...

Nature Cell Biology - This Perspective highlights the failures of an ageing cell in properly maintaining mRNA health at the various steps of the mRNA life cycle that result in vulnerability to...

Aberrant aggregation of the prion-like RNA binding protein TDP-43 drives several fatal neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS). In this work, we define how sho...

Fused in sarcoma (FUS) is an RNA-binding protein whose pathological aggregation via aberrant phase separation contributes to amyotrophic lateral sclerosis (ALS). Although RNA can modulate the phase b...

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive decline. Pathologically, AD is characterized by the accumulation of amyloid β (Aβ) monomers that may generate oligome...

Researchers show that a disease-causing Tau mutation disrupts the autophagy-lysosome pathway in human neurons, leading to Tau accumulation, and that enhancing autophagy can partially restore protein c...

Nature Structural & Molecular Biology, Published online: 31 March 2026; doi:10.1038/s41594-026-01785-9Liu et al. show that the C9orf72 GGGGCC-repeat RNA drives liquid-to-solid phase transition of poly(GR) in ALS/FTD through forming G-quadruplex and hairpin scaffolds, whereas targeting the RNA structures with small molecules reduces poly(GR) aggregation and cellular dysfunction.

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TDP-43 pathology is a hallmark of several neurodegenerative disorders, but the connection between TDP-43 aggregation and dysfunction remains poorly understood. This study develops a quantitative cell-...

Rhes-Slc4a7 membrane signaling drives TNT formation and mHTT spread, revealing a therapeutic target in Huntington disease.

TDP-43 pathology defines limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) and frequently co-occurs with Alzheimer’s disease neuropatholo…

Treatments that target a fragment of the mutant protein that causes Huntington's disease might be more effective than treatments—now in clinical trials—that target the whole protein but leave this fragment intact, a new study in mice suggests.

Jones Jagaraj et al. show that cofilin is hyperphosphorylated in postmortem spinal cord tissue from patients with sporadic ALS, disrupting actin dynamics a

FUS is an RNA/DNA-binding protein whose mislocalization and aggregation are defining pathological features of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Detectin...

Mast cells are immune cells that release membraneless mast cell extracellular granules (MCEGs) in response to allergic inflammation and pathogen infection. MCEGs are found to be condensates formed thr...

Nuclear speckles are key subnuclear structures that regulate gene expression in GC-rich regions. This work shows that the evolution and expansion of core speckle proteins were crucial for the increase...

Mapping of neurogenesis in human hippocampi across ages and different cognitive abilities using multiomic single-cell sequencing reveals distinct signatures between cognitive preservation and decline.

Myotonic dystrophy type 1 is a rare, dominantly inherited, progressive, disabling, neuromuscular disease that leads to decreased life expectancy and has no approved therapies. The disease is caused...

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

Liu et al. demonstrate that expanded C9orf72 G4C2 repeat RNAs bind gene promoters across the genome and form HQ structures with DNA. These structures obstruct key transcription machinery, repress gene...

INTRODUCTION The PSEN1E280A mutation causes autosomal dominant Alzheimer's disease (ADAD) with predictable onset, enabling presymptomatic studies. Extracellular vesicles (EVs) are emerging biomarker...

Despite advances in the fields of lipoplexes, metal nanoparticles, and other nucleic acid carriers, intracellular delivery of DNA/RNA therapeutics remains a ...

In ‘body-first’ Parkinson’s disease, misfolded proteins propagate from the gut’s nervous system to the brain. Immune-cell activity seems to play a key part in this spread.

This work establishes multigene RNA silencing as a viable therapeutic approach for Alzheimer’s disease. Bispecific antisense oligonucleotides produced strong, selective knockdown across multiple patho...