45 papers on TDP-43, STMN2 or UNC13A in ALS from the last ~18 months, pulled from PubMed on October 11, 2026. Top-journal papers come first, then reviews, then the newest.
Each summary is the authors' own conclusion, quoted from the PubMed abstract, not our interpretation. Lab and animal findings don't automatically carry over to people.
Liu J, Ong K, Meng A et al. · Acta neuropathologica · 2026 Oct 9 · PMID 42853426 · DOI
From the abstract:A detailed comparison of "dying-forward" and "dying-forward" is provided in the Discussion. The association of loss of axons and myelin with abnormal microglial activity shows glio-axonal interactions in UMN axon degeneration, the latter CST (lateral sclerosis) across all three spinal cord levels in the ALS UMN-p samples but does not establish a causal relationship.
Feole M, Devoto VMP, Dragišić N et al. · Acta neuropathologica · 2026 Oct 9 · PMID 42853422 · DOI
From the abstract:This could contribute to progressive accumulation of non-functional TDP-43 granules, disrupting mRNA trafficking and local translation. Our findings provide a foundation for understanding how physiological TDP-43 transport mechanisms may be impaired during disease, highlighting axonal TDP-43 transport pathways as potential therapeutic targets.
de Azevedo EM, Bernardo VS, Lima MMS et al. · Acta neuropathologica · 2026 Oct 6 · PMID 42837018 · DOI · Review
From the abstract:Collectively, the available evidence supports a shift from viewing SOD1 as a disease-specific protein to considering it a potential participant in interconnected proteopathic networks. Although the functional significance of SOD1 co-pathologies remains incompletely understood, elucidating the molecular basis of aggregation may provide new insights into disease onset and progression, improving our understanding of neu
Teunissen CE, Vermunt L, Barthélemy NR et al. · The Lancet. Neurology · 2026 Oct · PMID 42716045 · DOI · Review
From the abstract:Increased focus on biomarker-pathology relationships in experimental models will likely accelerate biomarker development and further the understanding of their precise substrates. Future clinical implementation of biomarkers to capture the full complexity of pathologies will likely be facilitated by the expansion of diagnostic methods, development of point of care technologies, and remote sampling approaches.
Spillman AM, Alsop EB, Gittings LM et al. · Acta neuropathologica · 2026 Sep 25 · PMID 42789089 · DOI
From the abstract:Consistent with TDP-43 loss-of-function pathology we identified cryptic exon (CE)-containing transcripts within C9-FTD frontal cortex-derived synaptosomes, including KALRN and STMN2, providing evidence that aberrantly spliced RNAs localize to synaptic compartments. Together, these findings define convergent molecular pathways underlying synapse vulnerability in both C9-FTD model systems and identify synaptic localiza
Codron P, Miranda M, Garnier M et al. · Acta neuropathologica · 2026 Sep 15 · PMID 42742812 · DOI · Review
From the abstract:It may also provide new opportunities for pathology-based biomarkers, therapeutic monitoring, and mechanistic studies aimed at understanding disease initiation and progression. However, current evidence is derived from small and methodologically heterogeneous cohorts, and peripheral pTDP-43 pathology is not restricted to ALS, emphasizing the need for larger standardized studies.
de Bertier S, Amador MD, Guissart C et al. · Acta neuropathologica · 2026 Sep 4 · PMID 42696048 · DOI
From the abstract:Nevertheless, together with previous studies, our findings support ARPP21 as an important ALS-associated gene, and indicate that both p.P529L/p.P563L and p.P713L/p.P747L should be considered pathogenic ALS-causing variants. Incorporating ARPP21 into the routine genetic testing panels for fALS could improve diagnostic yield.
Zhou Z, Luquette LJ, Dong G et al. · Cell · 2026 Sep 3 · PMID 42385702 · DOI
From the abstract:Rapid approach to DNA adduct recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes, and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represent a mechanism shared by both TDP-43 and tau neurodegeneration.
Compagnion AC, Ivanov A, Rana A et al. · Nature neuroscience · 2026 Aug · PMID 42420559 · DOI
From the abstract:It also led to cryptic exon inclusion in the Tyrobp mRNA, resulting in truncated DAP12 protein, thus causing defective TREM2 signaling. Our findings reveal a role for TDP-43 in regulating the TREM2-DAP12 axis in mice, highlighting a previously unrecognized mechanism through which TDP-43 controls microglial function.
Smith CL, Robinson JL, Lee EB · Acta neuropathologica · 2026 Jul 7 · PMID 42414528 · DOI · Review
From the abstract:We synthesize current knowledge of ANXA11's physiological roles in phase separation, membrane repair, and RNA granule dynamics, integrating emerging evidence on how disruption of these processes may promote pathological aggregation and toxicity. Finally, we outline priorities for future research, with particular emphasis on elucidating ANXA11's mechanistic connection to TDP-43.
Zhang Z, van Olst L, Alessandrini F et al. · Nature neuroscience · 2026 Jul · PMID 42135512 · DOI
From the abstract:Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.
Guo C, Chen K, Vatsavayai S et al. · Science translational medicine · 2026 Jun 3 · PMID 42234776 · DOI
From the abstract:Suppressing individual cryptic splicing events using antisense oligonucleotides partially restored neuronal function, and combined targeting almost fully rescued the synaptic deficit caused by TDP-43 loss. Together, our findings provide evidence that cryptic splicing in these synaptic and membrane excitability genes is not only a downstream marker but instead a direct driver of neuronal dysfunction, establishing a me
Ye Y, Zhang Z, Xiao Y et al. · Neuron · 2026 Jun 3 · PMID 41943580 · DOI
From the abstract:Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.
Hatano Y, Nakahara A, Tada M et al. · Acta neuropathologica · 2026 May 15 · PMID 42141160 · DOI
From the abstract:These findings indicate that APOE ε4 modifies the anatomical distribution of TDP-43 pathology in sporadic ALS through mechanisms independent of classical Alzheimer's disease pathology. Incorporation of APOE genotype into ALS stratification may be informative for biologically grounded subtype-specific therapeutic approaches.
Copley KE, Mauna JC, Danielson HL et al. · Science (New York, N.Y.) · 2026 May 7 · PMID 42096556 · DOI
From the abstract:In mice with cytoplasmic TDP-43 aggregation and motor neuron loss, an enhanced short RNA chaperone reduced pathological aggregation, restored TDP-43 function, and conferred neuroprotection. These results define a mechanistic and therapeutic framework for RNA-based strategies to counter TDP-43 proteinopathies.
Liu Y, Huang Z, Hsu YW et al. · Nature neuroscience · 2026 Apr · PMID 41912662 · DOI
From the abstract:ALS/FTD-linked UBQLN2 mutations and TAR DNA-binding protein 43 (TDP-43) pathology impair the degradation of ILVBL and ALDH3A2, leading to metabolic dysfunction and neurodegeneration. Restoring the UBQLN2-ILVBL/ALDH3A2 axis attenuates neurodegenerative phenotypes in neurons, organoids and mice, establishing UBQLN2 as a critical regulator of metabolic homeostasis in ALS/FTD and other related neurodegenerative diseases.
McLellan C, Campos-Melo D, Hammond R et al. · Acta neuropathologica · 2026 Mar 26 · PMID 41888437 · DOI
From the abstract:These findings support a model in which early or subtle disruptions, preceding visible pathology, may also contribute to miRNA downregulation in ALS. By identifying preserved miRNA networks as correlates of oculomotor neuron resilience in ALS, this work also exposes new therapeutic targets potentially capable of reinstating miRNA expression and reprogramming vulnerable SMNs.
Barone C, Wang R, Cooke S et al. · Acta neuropathologica · 2026 Mar 16 · PMID 41838122 · DOI
From the abstract:Notably, compensation for HK1 loss reduces cytoplasmic TDP-43 and ubiquitin accumulation, improves motor performance, and prolongs survival in TDP-43-associated ALS models. Together, these findings identify a previously unrecognized mechanism by which TDP-43 impairs glycolysis through HK1 misregulation and highlight glycolytic restoration as a potential therapeutic strategy in ALS.
Dubey SK, Chaubey D, Ikenaga C et al. · Neuron · 2026 Mar 4 · PMID 41475349 · DOI
From the abstract:Mechanistically, disease-associated mutations in VCP result in increased recruitment to NPCs through interactions with Ufd1-Npl4, leading to the removal of a subset of nucleoporins from NPCs and disrupting NCT. These findings show that the VCP-Ufd1-Npl4 pathway regulates NPC quality control and that disease-associated variants aberrantly activate the VCP-Ufd1-Npl4 complex to degrade NPCs and disrupt NCT.
Alessandrini F, Wright M, Kurosaki T et al. · Neuron · 2026 Feb 18 · PMID 41389796 · DOI
From the abstract:Transcriptomic analyses reveal convergent regulation of alternative polyadenylation and 3' UTR length by UPF1 and TDP-43, processes disrupted in ALS models and patient neurons. Our study defines the mRNA surveillance network of UPF1 in MNs and uncovers a link between RNA decay, TDP-43 dysfunction, and ALS neurodegeneration.
Jiang X, Schaeffer L, Patni D et al. · Science (New York, N.Y.) · 2026 Feb 5 · PMID 41643021 · DOI
From the abstract:Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell-derived neurons, which highlights the pot
Piol D, Khalil B, Robberechts T et al. · Nature neuroscience · 2026 Jan · PMID 41430470 · DOI
From the abstract:Axon-specific treatment with polyamine spermidine restores Eif5a hypusination and ameliorates mutant FUS-dependent neuronal defects, including suppression of local protein synthesis. Finally, in vivo spermidine treatment reduces ALS-related toxicity in mutant FUS and TDP-43 Drosophila models, which may have implications for therapy development.
Joseph BJ, Marshall KA, Harley P et al. · Nature neuroscience · 2025 Dec · PMID 41174170 · DOI
From the abstract:This event, which correlates with higher phosphorylated TDP-43 levels and earlier age of disease onset in patients, can be rescued by splice-modulating antisense oligonucleotides that dampen hyperexcitability in induced pluripotent stem cell cortical neurons and spinal motor neurons with TDP-43 depletion. Our work reveals that nuclear TDP-43 maintains the fidelity of KCNQ2 expression and function and provides a mecha
McEachin ZT, Chung M, Stratton SA et al. · Cell · 2025 Nov 13 · PMID 40865525 · DOI
From the abstract:Proteomic signatures in c9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundance that correlated with BIIB078 concentration was observed. Thus, despite widespread distribution, BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASO thera
Ghayal NB, Crook RJ, Jain A et al. · Acta neuropathologica · 2025 Nov 12 · PMID 41225259 · DOI
From the abstract:We thus demonstrated two novel ANXA11 proteinopathies strongly associated with FTLD-PLS, but not with TDP type C or pathogenic ANXA11 variants. Given the emerging relationship between TDP-43 and ANXA11 in neurodegenerative disease, we propose that TDP-43 and ANXA11 proteinopathy (TAP) comprises a distinct group of molecular pathologies and define three TAP types based on key clinical and neuropathologic characteristi
Bryce-Smith S, Brown AL, Chien MZYJ et al. · Nature neuroscience · 2025 Nov · PMID 41120751 · DOI
From the abstract:RNA sequencing (RNA-seq), thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) and ribosome profiling (Ribo-seq) revealed that distinct cryptic APA categories have different downstream effects on transcript levels and that cryptic 3'UTR extensions can increase RNA stability, leading to increased translation. In summary, we demonstrate that TDP-43 nuclear depletion induces cryptic APA, expanding
Zeng Y, Lovchykova A, Akiyama T et al. · Nature neuroscience · 2025 Nov · PMID 41120750 · DOI
From the abstract:APA events caused by loss of TDP-43 impact expression of disease-relevant genes (for example, SFPQ, NEFL and TMEM106B). These findings provide evidence that, in addition to cryptic exon inclusion, APA changes are a new facet of TDP-43 pathology.
Ionescu A, Ankol L, Ganapathy Subramaniam A et al. · Nature neuroscience · 2025 Nov · PMID 41044342 · DOI
From the abstract:Introducing miR-126 to SOD1G93A mice, primary co-cultures and human induced pluripotent stem cell (iPSC)-derived co-cultures with ALS mutations exhibits neuroprotective effects and delays motor decline. These findings identify a transcellular communication axis between muscles and motor neurons that regulates axonal local synthesis and NMJ maintenance, offering insights into ALS onset and progression.
García-Toledo I, Godoy-Corchuelo JM, Fernández-Beltrán LC et al. · Acta neuropathologica · 2025 Sep 4 · PMID 40906043 · DOI
From the abstract:We identified impaired cholesterol metabolism, mainly through the downregulation of endogenous cholesterol synthesis, alongside upregulated cholesterol transport pathways, which we further replicated in FTLD-TDP patients transcriptomic datasets. Collectively, our findings suggest that TDP-43 dysfunction disrupts brain cholesterol homeostasis, potentially compromising myelin integrity.
Mohammad SI, Vasudevan A, Oriquat G et al. · Behavioural brain research · 2027 Jan 5 · PMID 42697379 · DOI · Review
From the abstract:This review reviews the biogenesis, classification, isolation methods, and molecular content of EVs, and analyzes their role in the pathogenesis, diagnosis, and treatment of the most important neurodegenerative diseases. Also, the importance of EV-associated proteins, RNAs, and lipids as emerging diagnostic biomarkers, as well as the therapeutic potential of natural and engineered vesicles as drug delivery systems an
Morimoto S, Kato C, Takahashi S et al. · Regenerative therapy · 2026 Dec · PMID 42359165 · DOI · Review
From the abstract:The identification of STMN2 as a downstream target of TDP-43 dysfunction has opened a potential TDP-43-downstream nucleic acid therapeutic avenue for sporadic ALS, which constitutes approximately 90% of all cases, with company-reported interim data suggesting target engagement in the ongoing Phase 1/2 ANQUR trial (QRL-201). This review synthesizes the latest evidence across all three therapeutic domains, with attenti
Anastasakis DG, Hafner M · RNA biology · 2026 Dec · PMID 41964251 · DOI · Review
From the abstract:The same biophysical properties that make rG4s effective scaffolds for reversible phase separation in RNA processing, proteostasis, and acute stress become liabilities under chronic conditions: in ageing neurons, failure of rG4-protein homoeostasis transforms protective condensates into irreversible aggregates associated with α-synuclein, tau, TDP-43, and FUS pathology. We discuss the implications of a dynamic
Viljoen S, Chaves JCS, Peall I et al. · Journal of the neurological sciences · 2026 Nov 15 · PMID 42721706 · DOI · Review
From the abstract:This review provides a comprehensive assessment of known BBB/NVU dysfunction in ALS and methods of investigating this using in vitro and in vivo platforms with a focus on inflammation, oxidative stress and pathological TDP-43 expression. This review also presents a future perspective to overcoming barriers to treatment of ALS using new patient-derived BBB/NVU model systems.
Pattnaik PP, Prusty SK, Pati S et al. · Gene · 2026 Nov 15 · PMID 42476327 · DOI · Review
From the abstract:The common genetic basis and the cross-connecting molecular mechanisms of the various neurodegenerative diseases could help in the discovery of new biomarkers and pan-therapeutic targets. Further advances in molecular genetics, computational biology and precision medicine are needed to enhance early detection and the creation of effective disease-modifying treatments.
de La Seiglière H, Letourneur Æ, Ichas F et al. · Biophysical chemistry · 2026 Nov · PMID 42418847 · DOI · Review
From the abstract:We also examine the interplay of these proteins exploring how LLPS and condensate maturation could impinge on the emergence of co-pathologies contributing to disease progression. Finally we discuss emerging therapeutic strategies, aimed at modulating phase separation dynamics.
Inoue Y, Tanaka M, Oguchi T et al. · Brain research bulletin · 2026 Oct 15 · PMID 42727710 · DOI · Review
From the abstract:Integrating mechanisms of selective neuroprotection with translational neurobiological perspectives may provide a conceptual framework for ALS research. Leveraging preserved neural systems may not only inform biologically grounded supportive care strategies but also help identify mechanistically relevant targets for future disease-modifying interventions.
Choudhury A, Prabha S, Saeed MU et al. · Expert opinion on therapeutic targets · 2026 Oct 9 · PMID 42852552 · DOI · Review
From the abstract:Effective therapeutic discovery will require moving beyond single-target models toward ensemble-based validation strategies. Integrating structural biology, advanced imaging, biomarkers, and computational approaches may improve the identification of druggable targets and support precision-medicine-based interventions for neurodegenerative diseases.
Dahlhaus R, Yalcin I, Tischer J et al. · Neurobiology of disease · 2026 Oct 5 · PMID 42833594 · DOI · Review
From the abstract:In this review, we will therefore examine connections between TDP-43 and inner membrane systems, with a particular focus on nuclear and the ER membranes. In doing so, we will summarize evidence suggesting that the disease may have an early onset, potentially even prenatally, and describe how interactions between TDP-43 and the lipid metabolism as well as connections with membrane components, may drive cells towards A
Yu W, Zhao B, Ma M et al. · Brain, behavior, and immunity · 2026 Nov · PMID 42425169 · DOI
From the abstract:Glymphatic dysfunction and sleep impairment emerge as common pathological pathways across sexes. These findings highlight sex as a crucial biological variable shaping ALS heterogeneity and underscore the importance of incorporating sex-stratified analyses in future ALS neuroimmune research and clinical trials.
Viteri JA, Kerr NR, Brennan CD et al. · Neurobiology of disease · 2026 Oct 15 · PMID 42759848 · DOI
From the abstract:At the cellular level, cortical microglia were implicated as a potential mediator of senolytic benefits based on reduced microglial TDP-43 burden and senescence markers. Together, these findings identify cellular senescence as an early, disease-relevant, and modifiable feature of ALS pathology.
Butt TH, Strait M, Marcinczyk L et al. · Neurobiology of disease · 2026 Oct 15 · PMID 42722112 · DOI
From the abstract:Plasma ADEV pTDP-43/CD81 ratio best predicted ALS case status, with a mean AUC of 0.89 (95% CI: 0.75-0.99) from logistic models, corresponding to a mean sensitivity and specificity of 87% and 89%, respectively, and a mean AUC of 0.86 (95% CI: 0.82-0.90) from random forest models. Although the specificity of ADEV pTDP-43 relative to disease mimics and associations with disease progression require further investigation
Heinsinger N, Wang Y, Grauer S et al. · Neurobiology of disease · 2026 Oct 15 · PMID 42637106 · DOI
From the abstract:Furthermore, we confirmed that reducing Ataxin-2 levels via previously validated ASO delivery ameliorated TDP-43 pathology in rNLS8 mice. The discovery of ATXN2 alternative splicing, along with the confirmation of splicing modulation using ASOs in human cell-based assays, provides evidence for a proof-of-principle strategy to modulate Ataxin-2 protein levels for the treatment of ALS.
Ji C · Neuroscience · 2026 Oct 10 · PMID 42858780 · DOI
From the abstract:Cross-dataset similarities occur mainly among exploratory nominal targets and do not consistently extend to direction or magnitude. APA responses therefore show partial, context-dependent convergence rather than a universal defect.
Citrano KJ, Maheswari Jawahar VB, Reeves MM et al. · Cell reports. Medicine · 2026 Oct 9 · PMID 42854693 · DOI
From the abstract:To understand HDGFL2-CE as a readout of TDP-43 dysfunction, and its spatial relationship with TDP-43 pathology, we generate anti-HDGFL2-CE polyclonal and monoclonal antibodies and develop sensitive HDGFL2-CE immunoassays. With these tools, we observe that HDGFL2-CE accumulates in neurons with TDP-43 pathology, and that higher frontal cortex HDGFL2-CE in FTLD-TDP and FTLD-TDP/MND associates with greater pathological T