Search publications
16 results for “neurological disease”
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Single-cell and isoform-specific translational profiling of the mouse brain.
Nature · 2026
The brain displays the richest repertoire of post-transcriptional mechanisms regulating mRNA translation<sup>1-11</sup>. Among these, alternative splicing has been shown to drive cell-type specificity and, when disrupted, is strongly linked to neurological disorders<sup>12-17</sup>. However, genome-wide measurements of mRNA translation with isoform …
PMID 41708856 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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Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.
Cell reports · 2024 · 43(8): 114637
Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder …
PMID 39154337 DOI ↗
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Programmable macromolecule-based RNA-targeting therapies to treat human neurological disorders.
RNA (New York, N.Y.) · 2023 · 29(4): 489-497
Disruptions in RNA processing play critical roles in the pathogenesis of neurological diseases. In this Perspective, we discuss recent progress in the development of RNA-targeting therapeutic modalities. We focus on progress, limitations, and opportunities in a new generation of therapies …
PMID 36693761 DOI ↗
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Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose.
Journal of virology · 2021 · 95(5)
Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development …
PMID 33328307 DOI ↗
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Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies.
Critical reviews in biochemistry and molecular biology · 2021 · 56(1): 31-53
Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG<sub>50-3,500</sub> in <i>DMPK</i>; DM2, CCTG<sub>75-11,000</sub> in …
PMID 33172304 DOI ↗
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Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions.
Neuron · 2019 · 102(2): 294-320
RNA binding proteins are critical to the maintenance of the transcriptome via controlled regulation of RNA processing and transport. Alterations of these proteins impact multiple steps of the RNA life cycle resulting in various molecular phenotypes such as aberrant RNA …
PMID 30998900 DOI ↗
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Genetic mutations in RNA-binding proteins and their roles in ALS.
Human genetics · 2017 · 136(9): 1193-1214
Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of …
PMID 28762175 DOI ↗
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Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.
Molecular psychiatry · 2016 · 21(11): 1573-1588
Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined …
PMID 27698428 DOI ↗
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Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.
Genome medicine · 2016 · 8(1): 94
Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human …
PMID 27655340 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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A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
PloS one · 2014 · 9(12): e113258
The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …
PMID 25474699 DOI ↗
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ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.
Proceedings of the National Academy of Sciences of the United States of America · 2013 · 110(8): E736-45
Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, …
PMID 23382207 DOI ↗
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Genome-wide approaches to dissect the roles of RNA binding proteins in translational control: implications for neurological diseases.
Frontiers in neuroscience · 2012 · 6: 144
Translational control of messenger RNAs (mRNAs) is a key aspect of neurobiology, defects of which can lead to neurological diseases. In response to stimuli, local translation of mRNAs is activated at synapses to facilitate long-lasting forms of synaptic plasticity, the …
PMID 23060744 DOI ↗
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Genome-wide approaches in the study of microRNA biology.
Wiley interdisciplinary reviews. Systems biology and medicine · 2011 · 3(5): 491-512
MicroRNAs (miRNAs), a class of ∼21-23 nucleotide long non-coding RNAs (ncRNAs), have critical roles in diverse biological processes that encompass development, proliferation, apoptosis, stress response, and fat metabolism. miRNAs recognize their target mRNA transcripts by partial sequence complementarity and collectively …
PMID 21197653 DOI ↗
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Multiple layers of molecular controls modulate self-renewal and neuronal lineage specification of embryonic stem cells.
Human molecular genetics · 2008 · 17(R1): R67-75
Elucidating the molecular changes that arise during neural differentiation and fate specification is crucial for building accurate in vitro models of neurodegenerative diseases using human embryonic stem cells (hESCs). Here we review the importance of hESCs and derived progenitors in …
PMID 18632700 DOI ↗
Datasets 8
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [bulk RNA-seq]
Mus musculus · GPL24247
Distinct and shared molecular targets and functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [CLIP-Seq]
Mus musculus · GPL13112
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]
Homo sapiens · GPL11154
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [ATAC-seq]
Mus musculus · GPL24247
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_mouse]
Mus musculus · GPL13112
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array]
Mus musculus · GPL13185
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_Stability]
Homo sapiens · GPL11154
Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [Microglia RNA-seq]
Mus musculus · GPL24247
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