Jeffrey D. Rothstein

Direct mitochondrial import of lactate supports resilient carbohydrate oxidation

This study shows that lactate can be directly imported into mitochondria and oxidized to support cardiac energy production, independent of the pyruvate carrier.

Intrathecal (G4C2)149 delivery in C9orf72-deficient mice yields mild motor dysfunction and ALS/FTD pathological hallmarks

This paper delivers (G4C2)149 repeats intrathecally in C9orf72-deficient mice, revealing mild motor dysfunction and ALS/FTD pathological features.

Enterovirus D68 2A protease causes nuclear pore complex dysfunction and independently contributes to motor neuron toxicity

This study shows that EV-D68 2A protease disrupts nuclear pore complex function and causes motor neuron toxicity independently of viral replication.

Intact learning and memory in mice incapable of de novo myelination

This study shows that motor and fear learning in mice do not require newly formed myelin sheaths or rapid saltatory conduction, as Mbp-cKO mice with impaired myelination still learned and remembered normally.

Mutant SOD1 expressed by oligodendrocytes aggregates in myelinic nanochannels and accelerates disease progression in familial ALS mice

This study shows that mutant SOD1 aggregates in myelinic nanochannels and accelerates ALS progression in mice, highlighting the role of myelin channel integrity in disease.

Is SORL1 a common genetic target across neurodegenerative diseases?: A multi-ancestry biobank scale assessment

This study investigates the role of SORL1 genetic variants in AD, RD, and PD across diverse populations, identifying variants associated with risk but no significant cumulative effect.

Identification of molecular and clinical ALS subgroups based on TDP-43 loss of function molecular markers from population-based patient-derived iPS motor neurons

The paper identifies molecular and clinical subgroups of ALS using TDP-43 loss-of-function markers from patient-derived iPS motor neurons, revealing distinct disease severity and clinical outcomes.

Mapping the circulating proteome across neurodegeneration: A harmonized, consortium-scale framework for uncovering molecular pathophysiology

The paper presents a harmonized framework for analyzing large-scale plasma proteomics data across neurodegenerative diseases, identifying disease-specific circulating signatures and biomarkers.

Astrocyte MCT1 expression does not contribute to the axonal degenerative phenotype observed with ubiquitous MCT1 depletion.

This study shows that astrocyte MCT1 depletion does not cause axonal degeneration, unlike oligodendrocyte MCT1 depletion, suggesting astrocyte MCT1 is not essential for axonal energy homeostasis with aging.

Divergent and Convergent TMEM106B Pathology in Murine Models of Neurodegeneration and Human Disease

The paper compares TMEM106B pathology in murine models of neurodegenerative diseases to human postmortem tissue, identifying differences and convergent links to TDP-43 and Tau pathology.

Visualizing nuclear pore complex plasticity with pan-Expansion Microscopy

This paper introduces pan-Expansion Microscopy to visualize nuclear pore complex plasticity, revealing LINC complex-dependent diameter biases and nucleoporin repositioning in an ALS model.

Biobank-scale characterization of Alzheimer's disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers across diverse ancestries

A robust evaluation of TDP-43, poly GP, cellular pathology, and behavior in a AAV-C9ORF72 (G4C2)66 mouse model

This study evaluates a mouse model of C9-ALS/FTD, finding it robust for molecular mechanisms but not for neurodegeneration and motor deficits.

Counter-regulation of RNA stability by UPF1 and TDP43

The paper develops NMDq, a next-generation sequencing method to quantify NMD status, and applies it to ALS and FTD, finding no significant PTC differences but showing UPF1 regulates RNA homeostasis through alternative polyadenylation.

Highly variable molecular signatures of TDP-43 loss of function are associated with nuclear pore complex injury in a population study of sporadic ALS patient iPSNs

Disease related changes in ATAC-Seq of more than 450 iPSC-derived motor neuron lines from ALS patients and controls

The paper analyzes ATAC-seq data from iPSC-derived motor neurons of ALS patients and controls to identify disease-specific chromatin accessibility changes and their predictive power for disease progression.

G2C4 targeting antisense oligonucleotides potently mitigate TDP-43 dysfunction in C9orf72 ALS/FTD human neurons

This study shows that targeting G2C4 antisense repeat RNA, not G4C2 sense RNA, mitigates TDP-43 dysfunction in C9orf72 ALS/FTD patient neurons, explaining the failure of previous G4C2 ASO clinical trials.

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

The paper performs an integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients to identify dysregulated pathways and validate them in vivo and in postmortem data.

G4C2 repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD

The paper identifies POM121 as a critical nucleoporin affected by C9orf72 repeat RNA, leading to nuclear pore complex disassembly and neuronal toxicity in ALS/FTD.

Monocarboxylate transporter 1 in Schwann cells is critical for maintenance of sensory nerve myelination during aging

This study shows that MCT1 in Schwann cells is essential for maintaining sensory nerve myelination during aging, leading to hypomyelination and impaired function.