Isacson et al. describe a paradigm shift in understanding Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease, moving beyond proteinopathy-centered observations toward primary lipid and metabolic disturbances. The perspective explores how deeper insights into cell biology and brain health may enable innovative therapeutic interventions against neurodegeneration.

Read the full paper: Nucleoporin 50 rescues hallmarks of TDP-43 proteinopathy in ALS/FTD disease models

Alzheimer’s disease (AD) has traditionally been viewed as a central nervous system (CNS)-restricted proteinopathy. Although this neurocentric focus has yielded fundamental insights; it may not fully c...

Alzheimer’s disease (AD) has traditionally been viewed as a central nervous system (CNS)-restricted proteinopathy. Although this neurocentric focus has yielded fundamental insights; it may not fully c...

The misfolded aggregation of TDP-43 protein is a hallmark of several neurodegenerative diseases. This study shows that silencing the Drosophila homolog of NONO, a paraspeckle component, worsens TDP-4...

We read with interest the study by Wong et al., which reports an observational association between glaucoma and subsequent neurodegenerative diagnoses, with associations varying by age at diagnosis and glaucoma subtype1. The authors correctly highlight that these findings indicate population-level associations rather than causal links, and they explore possible shared mechanisms such as vascular pathology and proteinopathy. Mitochondrial dysfunction is mentioned briefly in relation to primary open-angle glaucoma (POAG) and the lamina cribrosa.

Minimally disruptive genetic code expansion enables faithful, site-specific labeling of G3BP1 and TDP-43, revealing native stress granule dynamics and ALS-linked protein behavior in live cells.

Minimally disruptive genetic code expansion enables faithful, site-specific labeling of G3BP1 and TDP-43, revealing native stress granule dynamics and ALS-linked protein behavior in live cells.

Post-viral neurological syndromes, such as post-acute sequelae of COVID-19, present a paradox of severe symptoms despite minimal CNS viral replication…

INTRODUCTION Transactive response DNA-binding protein 43 (TDP-43) proteinopathy is associated with frontotemporal dementia and Alzheimer's disease (AD). We previously demonstrated that synapsin-prom...

Multisystem proteinopathy 1 (MSP1), caused by gain-of-function VCP variants, leads to multisystem degeneration. Using VCP patient-derived hiPSCs, skeletal muscle progenitor cells were generated to ev....

The authors report that the presynaptic protein bassoon forms toxic aggregates in neuronal somata in multiple sclerosis. Stimulation of proteasomal activity reduces bassoon aggregates, neuroaxonal los...

Aberrant phase separation- and stress granule (SG)-mediated cytosolic aggregation of TDP-43 in motor neurons is the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we found that graphene quantum dots (GQDs) potentially modulate TDP-43 aggregation during SG dynamics and phase separation. The intrinsically disordered region in the C-terminus of TDP-43 exhibited amyloid fibril formation; however, GQDs inhibited the formation of amyloid fibrils through direct intermolecular interactions with TDP-43. These effects were accompanied by attenuation of the ALS phenotype in animal models. Additionally, GQDs delayed the onset and survival of TDP-43 transgenic mouse models by enhancing motor neuron survival, reducing glial activation, and reducing the cytosolic aggregation of TDP-43 in motor neurons. In this research, we demonstrated the efficacy of GQDs on the SG-mediated aggregation of TDP-43 and the binding property of GQDs with TDP-43. Additionally, we demonstrated the clinical feasibility of GQDs using several animal models and other types of ALS caused by FUS and C9orf72. Therefore, GQDs could offer a new therapeutic approach for proteinopathy-associated ALS.

Post-viral neurological syndromes, such as post-acute sequelae of COVID-19, present a paradox of severe symptoms despite minimal CNS viral replication…