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16 results for “Neurodegeneration”
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RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.
Trends in cell biology · 2026
In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging …
PMID 42711219 DOI ↗
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The YTHDF proteins modulate Alzheimer's disease-associated brain gene signatures.
Molecular neurodegeneration · 2026 · 21(1)
Gene signatures of Alzheimer's disease (AD) brains reflect the output of a complex interplay of genetic, epigenetic, epi-transcriptomic, and post-transcriptional regulations. To nominate candidate factors modulating these signatures, we developed a machine learning model to integrate cellular and molecular features …
PMID 42811341 DOI ↗
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Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.
Nature communications · 2025 · 16(1): 7690
Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of …
PMID 40825784 DOI ↗
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RNA triggers chronic stress during neuronal aging.
bioRxiv : the preprint server for biology · 2025
Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from several sources, but there is significant disagreement about which stress might contribute to aging …
PMID 40799579 DOI ↗
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Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.
Nature neuroscience · 2025 · 28(6): 1174-1184
Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged …
PMID 40456907 DOI ↗
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Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.
Nature communications · 2024 · 15(1): 10796
Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal …
PMID 39737952 DOI ↗
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Localized synthesis of molecular chaperones sustains neuronal proteostasis.
bioRxiv : the preprint server for biology · 2024
Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted …
PMID 37873158 DOI ↗
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Aging RNA granule dynamics in neurodegeneration.
Frontiers in molecular biosciences · 2022 · 9: 991641
Disordered RNA-binding proteins and repetitive RNA sequences are the main genetic causes of several neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease. Importantly, these components also seed the formation of cytoplasmic liquid-like granules, like stress granules and P bodies. …
PMID 36188213 DOI ↗
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Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.
PLoS genetics · 2019 · 15(3): e1007948
Glial cells regulate multiple aspects of synaptogenesis. In the absence of Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using a genetic approach, we show that neural activity-regulated negative factors produced by muscle …
PMID 30870413 DOI ↗
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Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
Acta neuropathologica · 2018 · 136(3): 405-423
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …
PMID 29881994 DOI ↗
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Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.
Cell · 2018 · 172(3): 590-604.e13
Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, …
PMID 29373831 DOI ↗
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Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.
Nature genetics · 2017 · 49(3): 457-464
Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg<sup>2+</sup>-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) …
PMID 28092684 DOI ↗
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Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.
Neuron · 2016 · 92(4): 780-795
HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …
PMID 27773581 DOI ↗
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PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.
Nature medicine · 2016 · 22(1): 37-45
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT …
PMID 26642438 DOI ↗
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RNA-binding proteins in neurodegeneration: Seq and you shall receive.
Trends in neurosciences · 2015 · 38(4): 226-36
As critical players in gene regulation, RNA binding proteins (RBPs) are taking center stage in our understanding of cellular function and disease. In our era of bench-top sequencers and unprecedented computational power, biological questions can be addressed in a systematic, …
PMID 25765321 DOI ↗
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Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience · 2007 · 27(22): 5869-78
Diet and exercise have a profound impact on brain function. In particular, natural nutrients found in plants may influence neuronal survival and plasticity. Here, we tested whether consumption of a plant-derived flavanol, (-)epicatechin, enhances cognition in sedentary or wheel-running female …
PMID 17537957 DOI ↗
Datasets 20
Modulation of the DNA/RNA Binding Protein ARID5A Regulates Microglial Activation and Response [RIP-Seq]
Homo sapiens · Illumina
Modulation of the DNA/RNA Binding Protein ARID5A Regulates Microglial Activation and Response [eclip]
Homo sapiens · Illumina
Modulation of the DNA/RNA Binding Protein ARID5A Regulates Microglial Activation and Response [cutnrun]
Homo sapiens · Illumina
Modulation of the DNA/RNA Binding Protein ARID5A Regulates Microglial Activation and Response [rna-seq]
Homo sapiens · Illumina
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal
Mus musculus · GPL13112
Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration
Homo sapiens · GPL20301
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Homo sapiens · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [eCLIP-seq]
Mus musculus · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNASeq, RiboSeq]
Homo sapiens · GPL24676
Mitochondrial double-stranded RNA triggers chronic stress in aged neurons
Homo sapiens · GPL24676, GPL30173
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_small_rnaseq]
Mus musculus · GPL15520
Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress
Homo sapiens · GPL20301
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_2]
Homo sapiens · GPL15106
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [iCLIP-seq]
Mus musculus · GPL13112
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_1]
Homo sapiens · GPL15106
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_RNA-seq_mouse_SC]
Mus musculus · GPL13112
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_Stress]
Homo sapiens · GPL17585
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_mouse_SC]
Mus musculus · GPL13185
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_eCLIP_human_iPSC_MN]
Homo sapiens · GPL16791
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_ASO]
Homo sapiens · GPL17585
Analyses 1
GSE122069 · 2 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)