Sami J. Barmada

Cerebrospinal fluid YWHAG:NPTX2 ratio predicts clinical severity and future phenoconversion in frontotemporal lobar degeneration

The paper identifies the CSF YWHAG:NPTX2 ratio as a biomarker for predicting clinical severity and phenoconversion in FTLD, showing strong correlation with disease progression and improved trial design potential.

CTE-Type Tau Filaments in Alzheimer's Disease with Co-morbid LATE-NC

The paper determines the structure of tau filaments in Alzheimer's disease patients with co-morbid LATE-NC using cryo-electron microscopy, revealing a CTE-type tau fold in addition to the Alzheimer's fold.

ADAR2-Mediated RNA Editing Promotes TDP-43 Nuclear Export and Alters RNA Binding

This study shows ADAR2-mediated RNA editing promotes TDP-43 nuclear export and alters its RNA binding, contributing to neurodegenerative disease mechanisms.

Neurodegeneration risk variants promote lysosomal TMEM106B fibrilaccumulation

The paper identifies TMEM106B fibril accumulation as a shared mechanism in neurodegeneration linked to genetic variants in TMEM106B and GRN.

VISTA-FISH: Video Imaging with Spatial-Temporal Analysis by Fluorescent In Situ Hybridization

VISTA-FISH links live-cell imaging with gene expression in neurons to study differentiation and cellular activity.

An autism spectrum disorder mutation in Topoisomerase 3B causes accumulation of covalent mRNA intermediates by disrupting metal binding within the zinc finger domain

This study shows that an autism-linked TOP3B mutation causes mRNA covalent intermediates by disrupting metal binding in the zinc finger domain, leading to neuronal toxicity.

Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation

The paper identifies cryptic intronic C9orf72 transcripts as endogenous templates for RAN translation, leading to DPR production in ALS/FTD.

Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS

This study shows NLK disrupts nuclear import, causing TDP43 mislocalization in ALS, and suggests NLK as a therapeutic target.

Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and alter their functional properties

This study shows that endogenous retrovirus-like proteins RTL8 and PEG10 regulate UBQLN2's recruitment to stress granules and alter their functional properties.

AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons

This study shows that AAGGG repeat expansions cause synaptic defects in CANVAS neurons independently of RFC1, with phenotypes corrected by repeat deletion.

Molecular Visualization of Neuronal TDP43 Pathology In Situ

This study uses a multimodal cryo-correlative microscopy pipeline to visualize TDP43 mislocalization and aggregation in iPSC-derived neurons and patient tissue, revealing ordered fibrils in autophagosomes and lysosomes.

Stress granule formation helps to mitigate neurodegeneration

This study investigates the role of stress granule formation in neurodegeneration, finding that reducing stress granules exacerbates disease phenotypes in models of ataxia, ALS, and FTD.

TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms

This study identifies TDP43 autoregulation as a source of shortened isoforms, showing they are regulated by NMD and post-translational degradation, and their dysregulation leads to neurodegeneration.

Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats

The paper shows that ribosomal quality control factors reduce toxic repeat-associated non-AUG translation from GC-rich repeats by preventing ribosomal stalling.

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.

RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia

This study shows that RNA methylation influences TDP43 binding and contributes to neurodegeneration in ALS by modulating RNA stability and TDP43 function.

Myotubularin-related phosphatase 5 is a critical determinant of autophagy in neurons

This study identifies MTMR5 as a neuron-specific autophagy suppressor, showing its role in limiting autophagy and its potential as a therapeutic target for neurodegenerative diseases.

Neuronal activity regulates Matrin 3 levels and function in a calcium-dependent manner through calpain cleavage and calmodulin binding

This study shows that neuronal activity regulates MATR3 levels and function through calpain cleavage and Ca2+/calmodulin binding, linking these processes to ALS pathology.

Enhanced detection of nucleotide repeat mRNA with hybridization chain reaction

This study compares hybridization chain reaction (HCR) to FISH for detecting repeat RNA foci in neurodegenerative disorders, finding HCR to be significantly more sensitive.

Inhibiting glycogen synthase kinase 3 suppresses TDP-43-mediated neurotoxicity in a caspase-dependant manner

This study shows that inhibiting GSK3 reduces TDP-43 levels and neurotoxicity in mammalian neurons by promoting TDP-43 turnover through a caspase-dependent mechanism.

TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD

This study shows TDP-43 stabilizes G3BP1 transcripts via direct binding, and TDP-43 depletion reduces G3BP1 protein levels, contributing to stress granule dysfunction in ALS/FTD.

The carboxyl-termini of RAN translated GGGGCC nucleotide repeat expansions modulate toxicity in models of ALS/FTD

This paper shows that the carboxyl-termini of RAN translated DPRs from GGGGCC repeats affect toxicity in ALS/FTD models, with GR DPRs showing greater toxicity due to their unstructured C-termini.

Shortened TDP43 isoforms upregulated by neuronal hyperactivity drive TDP43 pathology in ALS

This study shows that shortened TDP43 isoforms, upregulated by neuronal hyperactivity, drive TDP43 pathology in ALS by forming cytoplasmic inclusions and sequestering full-length TDP43.

Sema3A Facilitates a Retrograde Death Signal via CRMP4-Dynein Complex Formation in ALS Motor Axons

The paper identifies a novel retrograde death signal mechanism in ALS motor neurons involving CRMP4-dynein complex formation triggered by muscle-secreted Sema3A.