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  1. Article ; Online: Elevated FUS levels by overriding its autoregulation produce gain-of-toxicity properties that disrupt protein and RNA homeostasis.

    Ho, Wan Yun / Ling, Shuo-Chien

    Autophagy

    2019  Volume 15, Issue 9, Page(s) 1665–1667

    Abstract: Coding or non-coding mutations in FUS (fused in sarcoma) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition to familial ALS, abnormal aggregates of FUS are present in a portion of FTD and other neurodegenerative ... ...

    Abstract Coding or non-coding mutations in FUS (fused in sarcoma) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition to familial ALS, abnormal aggregates of FUS are present in a portion of FTD and other neurodegenerative diseases independent of their mutations. Broad expression within the central nervous system of either wild-type or two ALS-linked human FUS mutants produces progressive motor phenotypes accompanied by characteristic ALS-like pathology. FUS levels are autoregulated to maintain an optimal steady-state level. Increasing FUS expression by saturating its autoregulatory mechanism results in rapidly progressive neurological phenotypes and dose-dependent lethality. Genome-wide expression analysis reveals genetic mis-regulations distinct from those via FUS reduction. Among these are increased expression of lysosomal proteins, suggestive of disruption in protein homeostasis as a potential gain-of-toxicity mechanism. Indeed, increased expression of wild-type FUS or ALS-linked mutant forms of FUS inhibit macroautophagy/autophagy. Collectively, our results demonstrate that: (1) mice expressing FUS develop progressive motor deficits, (2) increased FUS expression by overriding its autoregulatory mechanism accelerates neurodegeneration, providing a basis for FUS involvement without mutation, and (3) disruption in both protein homeostasis and RNA processing contribute to FUS-mediated toxicity.
    MeSH term(s) Amyotrophic Lateral Sclerosis ; Animals ; Autophagy ; Homeostasis ; Humans ; Mice ; Mutation ; RNA ; RNA-Binding Protein FUS/genetics
    Chemical Substances FUS protein, human ; RNA-Binding Protein FUS ; RNA (63231-63-0)
    Language English
    Publishing date 2019-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2019.1633162
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  2. Article ; Online: Cholesterol dyshomeostasis in amyotrophic lateral sclerosis: cause, consequence, or epiphenomenon?

    Hartmann, Hannelore / Ho, Wan Yun / Chang, Jer-Cherng / Ling, Shuo-Chien

    The FEBS journal

    2021  

    Abstract: Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease, is characterized by the selective degeneration of motor neurons leading to paralysis and eventual death. Multiple pathogenic mechanisms, including systemic ... ...

    Abstract Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disease, is characterized by the selective degeneration of motor neurons leading to paralysis and eventual death. Multiple pathogenic mechanisms, including systemic dysmetabolism, have been proposed to contribute to ALS. Among them, dyslipidemia, i.e., abnormal level of cholesterol and other lipids in the circulation and central nervous system (CNS), has been reported in ALS patients, but without a consensus. Cholesterol is a constituent of cellular membranes and a precursor of steroid hormones, oxysterols, and bile acids. Consequently, optimal cholesterol levels are essential for health. Due to the blood-brain barrier (BBB), cholesterol cannot move between the CNS and the rest of the body. As such, cholesterol metabolism in the CNS is proposed to operate autonomously. Despite its importance, it remains elusive how cholesterol dyshomeostasis may contribute to ALS. In this review, we aim to describe the current state of cholesterol metabolism research in ALS, identify unresolved issues, and provide potential directions.
    Language English
    Publishing date 2021-09-01
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2173655-8
    ISSN 1742-4658 ; 1742-464X
    ISSN (online) 1742-4658
    ISSN 1742-464X
    DOI 10.1111/febs.16175
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    Zs.A 260: Show issues Location:
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  3. Article ; Online: Deregulated expression of a longevity gene, Klotho, in the C9orf72 deletion mice with impaired synaptic plasticity and adult hippocampal neurogenesis.

    Ho, Wan Yun / Navakkode, Sheeja / Liu, Fujia / Soong, Tuck Wah / Ling, Shuo-Chien

    Acta neuropathologica communications

    2020  Volume 8, Issue 1, Page(s) 155

    Abstract: Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72- ... ...

    Abstract Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72-mediated pathogenesis. However, how loss of C9orf72 impacts neuronal and synaptic functions remains undetermined. Here, we showed that long-term potentiation at the dentate granule cells and long-term depression at the Schaffer collateral/commissural synapses at the area CA1 were reduced in the hippocampus of C9orf72 knockout mice. Using unbiased transcriptomic analysis, we identified that Klotho, a longevity gene, was selectively dysregulated in an age-dependent manner. Specifically, Klotho protein expression in the hippocampus of C9orf72 knockout mice was incorrectly enriched in the dendritic regions of CA1 with concomitant reduction in granule cell layer of dentate gyrus at 3-month of age followed by an accelerating decline during aging. Furthermore, adult hippocampal neurogenesis was reduced in C9orf72 knockout mice. Taken together, our data suggest that C9ORF72 is required for synaptic plasticity and adult neurogenesis in the hippocampus and Klotho deregulations may be part of C9ORF72-mediated toxicity.
    MeSH term(s) Animals ; C9orf72 Protein/deficiency ; Glucuronidase/metabolism ; Hippocampus/metabolism ; Hippocampus/pathology ; Mice ; Mice, Knockout ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurogenesis/physiology ; Neuronal Plasticity/physiology ; Transcriptome
    Chemical Substances C9orf72 Protein ; C9orf72 protein, mouse ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31)
    Keywords covid19
    Language English
    Publishing date 2020-09-04
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-020-01030-4
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  4. Article ; Online: The vulnerability of motor and frontal cortex-dependent behaviors in mice expressing ALS-linked mutation in TDP-43.

    Wong, Peiyan / Ho, Wan Yun / Yen, Yi-Chun / Sanford, Emma / Ling, Shuo-Chien

    Neurobiology of aging

    2020  Volume 92, Page(s) 43–60

    Abstract: TDP-43 aggregates are the defining pathological hallmark for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Strikingly, these TDP-43 proteinopathies are also found in other neurodegenerative diseases, including Alzheimer's disease ...

    Abstract TDP-43 aggregates are the defining pathological hallmark for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Strikingly, these TDP-43 proteinopathies are also found in other neurodegenerative diseases, including Alzheimer's disease and are prevalent in the brains of old-aged humans. Furthermore, disease-causal mutations in TDP-43 have been identified for ALS and FTD. Collectively, the evidence indicates that TDP-43 dysfunctions lead to motor and cognitive deficits. To determine whether the mouse line expressing an ALS-linked mutation in TDP-43 (Q331K) can be used to study ALS-FTD spectrum disorders, we performed a systematic and longitudinal behavioral assessment that covered motor and cognitive functions. Deficits in motor and cognitive abilities were observed as early as 3 months of age and persisted through to 12 months of age. Within the cognitive modalities, the hippocampus-mediated spatial learning and memory, and contextual fear conditioning, were normal; whereas the frontal cortex-mediated working memory and cognitive flexibility were impaired. Biochemically, the human TDP-43 transgene downregulates endogenous mouse TDP-43 mRNA and protein, resulting in human TDP-43 protein that is comparable with the physiological level in cerebral cortex and hippocampus. Furthermore, Q331K TDP-43 is largely retained at the nucleus without apparent aggregates. Taken together, our data suggest that motor and frontal cortex may be more vulnerable to disease-linked mutation in TDP-43 and, this mouse model may be used to assess ALS-FTD-related spectrum diseases and the molecular underpinnings associated with the phenotypes.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Cognition ; DNA-Binding Proteins/genetics ; Disease Models, Animal ; Female ; Frontal Lobe/physiopathology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Activity ; Motor Cortex/physiopathology ; Mutation
    Chemical Substances DNA-Binding Proteins ; TARDBP protein, human
    Language English
    Publishing date 2020-04-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2020.03.019
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  5. Article: Deregulated expression of a longevity gene, Klotho, in the C9orf72 deletion mice with impaired synaptic plasticity and adult hippocampal neurogenesis

    Ho, Wan Yun / Navakkode, Sheeja / Liu, Fujia / Soong, Tuck Wah / Ling, Shuo-Chien

    Acta Neuropathol Commun

    Abstract: Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72- ... ...

    Abstract Hexanucleotide repeat expansion of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Synergies between loss of C9ORF72 functions and gain of toxicities from the repeat expansions contribute to C9ORF72-mediated pathogenesis. However, how loss of C9orf72 impacts neuronal and synaptic functions remains undetermined. Here, we showed that long-term potentiation at the dentate granule cells and long-term depression at the Schaffer collateral/commissural synapses at the area CA1 were reduced in the hippocampus of C9orf72 knockout mice. Using unbiased transcriptomic analysis, we identified that Klotho, a longevity gene, was selectively dysregulated in an age-dependent manner. Specifically, Klotho protein expression in the hippocampus of C9orf72 knockout mice was incorrectly enriched in the dendritic regions of CA1 with concomitant reduction in granule cell layer of dentate gyrus at 3-month of age followed by an accelerating decline during aging. Furthermore, adult hippocampal neurogenesis was reduced in C9orf72 knockout mice. Taken together, our data suggest that C9ORF72 is required for synaptic plasticity and adult neurogenesis in the hippocampus and Klotho deregulations may be part of C9ORF72-mediated toxicity.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32887666
    Database COVID19

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  6. Article ; Online: TDP-43 maximizes nerve conduction velocity by repressing a cryptic exon for paranodal junction assembly in Schwann cells.

    Chang, Kae-Jiun / Agrawal, Ira / Vainshtein, Anna / Ho, Wan Yun / Xin, Wendy / Tucker-Kellogg, Greg / Susuki, Keiichiro / Peles, Elior / Ling, Shuo-Chien / Chan, Jonah R

    eLife

    2021  Volume 10

    Abstract: TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic ... ...

    Abstract TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic delay in peripheral nerve conduction causing significant motor deficits in mice, which is directly attributed to the absence of paranodal axoglial junctions. By contrast, paranodes in the central nervous system are unaltered in oligodendrocytes lacking TDP-43. Mechanistically, TDP-43 binds directly to
    MeSH term(s) Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Exons ; Female ; Intercellular Junctions/metabolism ; Male ; Mice ; Neural Conduction ; Schwann Cells/metabolism
    Chemical Substances DNA-Binding Proteins ; TDP-43 protein, mouse
    Language English
    Publishing date 2021-03-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.64456
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  7. Article ; Online: FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons.

    Ho, Wan Yun / Chak, Li-Ling / Hor, Jin-Hui / Liu, Fujia / Diaz-Garcia, Sandra / Chang, Jer-Cherng / Sanford, Emma / Rodriguez, Maria J / Alagappan, Durgadevi / Lim, Su Min / Cho, Yik-Lam / Shimizu, Yuji / Sun, Alfred Xuyang / Tyan, Sheue-Houy / Koo, Edward / Kim, Seung Hyun / Ravits, John / Ng, Shi-Yan / Okamura, Katsutomo /
    Ling, Shuo-Chien

    iScience

    2023  Volume 26, Issue 11, Page(s) 108152

    Abstract: MicroRNAs (miRNAs) modulate mRNA expression, and their deregulation contributes to various diseases including amyotrophic lateral sclerosis (ALS). As fused in sarcoma (FUS) is a causal gene for ALS and regulates biogenesis of miRNAs, we systematically ... ...

    Abstract MicroRNAs (miRNAs) modulate mRNA expression, and their deregulation contributes to various diseases including amyotrophic lateral sclerosis (ALS). As fused in sarcoma (FUS) is a causal gene for ALS and regulates biogenesis of miRNAs, we systematically analyzed the miRNA repertoires in spinal cords and hippocampi from ALS-FUS mice to understand how FUS-dependent miRNA deregulation contributes to ALS. miRNA profiling identified differentially expressed miRNAs between different central nervous system (CNS) regions as well as disease states. Among the up-regulated miRNAs, miR-1197 targets the pro-survival pseudokinase
    Language English
    Publishing date 2023-10-06
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108152
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  8. Article ; Online: Cell-autonomous requirement of TDP-43, an ALS/FTD signature protein, for oligodendrocyte survival and myelination.

    Wang, Jia / Ho, Wan Yun / Lim, Kenneth / Feng, Jia / Tucker-Kellogg, Greg / Nave, Klaus-Armin / Ling, Shuo-Chien

    Proceedings of the National Academy of Sciences of the United States of America

    2018  Volume 115, Issue 46, Page(s) E10941–E10950

    Abstract: TDP-43 aggregates in neurons and glia are the defining pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), raising the possibility of glial damage in the disease pathogenesis. However, the normal physiological ... ...

    Abstract TDP-43 aggregates in neurons and glia are the defining pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), raising the possibility of glial damage in the disease pathogenesis. However, the normal physiological functions of TDP-43 in glia are largely unknown. To address how TDP-43 may be required for oligodendroglial functions we selectively deleted TDP-43 in mature oligodendrocytes in mice. Although mice with TDP-43 deleted in oligodendrocytes are born in an expected Mendelian ratio, they develop progressive neurological phenotypes leading to early lethality accompanied by a progressive reduction in myelination. The progressive myelin reduction is likely due to a combination of the cell-autonomous RIPK1-mediated necroptosis of mature oligodendrocytes and the TDP-43-dependent reduction in the expression of myelin genes. Strikingly, enhanced proliferation of NG2-positive oligodendrocyte precursor cells within the white matter, but not the gray matter, was able to replenish the loss of mature oligodendrocytes, indicating an intrinsic regeneration difference between the gray and white matter oligodendrocytes. By contrast, there was no loss of spinal cord motor neurons and no sign of denervation at the neuromuscular synapses. Taken together, our data demonstrate that TDP-43 is indispensable for oligodendrocyte survival and myelination, and loss of TDP-43 in oligodendrocytes exerts no apparent toxicity on motor neurons.
    MeSH term(s) Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Animals ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Disease Models, Animal ; Female ; Frontotemporal Dementia/metabolism ; Frontotemporal Dementia/pathology ; Gray Matter/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Motor Neurons/cytology ; Motor Neurons/metabolism ; Myelin Sheath/genetics ; Myelin Sheath/metabolism ; Nerve Fibers, Myelinated/metabolism ; Neuroglia/cytology ; Neuroglia/metabolism ; Oligodendroglia/cytology ; Oligodendroglia/metabolism ; Spinal Cord/metabolism ; White Matter/metabolism
    Chemical Substances DNA-Binding Proteins ; TDP-43 protein, mouse
    Language English
    Publishing date 2018-10-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1809821115
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    Zs.A 1148: Show issues Location:
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  9. Article ; Online: Dysfunction in nonsense-mediated decay, protein homeostasis, mitochondrial function, and brain connectivity in ALS-FUS mice with cognitive deficits.

    Ho, Wan Yun / Agrawal, Ira / Tyan, Sheue-Houy / Sanford, Emma / Chang, Wei-Tang / Lim, Kenneth / Ong, Jolynn / Tan, Bernice Siu Yan / Moe, Aung Aung Kywe / Yu, Regina / Wong, Peiyan / Tucker-Kellogg, Greg / Koo, Edward / Chuang, Kai-Hsiang / Ling, Shuo-Chien

    Acta neuropathologica communications

    2021  Volume 9, Issue 1, Page(s) 9

    Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of the same disease spectrum of adult-onset neurodegenerative diseases that affect the motor and cognitive functions, respectively. Multiple common genetic loci such ...

    Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of the same disease spectrum of adult-onset neurodegenerative diseases that affect the motor and cognitive functions, respectively. Multiple common genetic loci such as fused in sarcoma (FUS) have been identified to play a role in ALS and FTD etiology. Current studies indicate that FUS mutations incur gain-of-toxic functions to drive ALS pathogenesis. However, how the disease-linked mutations of FUS affect cognition remains elusive. Using a mouse model expressing an ALS-linked human FUS mutation (R514G-FUS) that mimics endogenous expression patterns, we found that FUS proteins showed an age-dependent accumulation of FUS proteins despite the downregulation of mouse FUS mRNA by the R514G-FUS protein during aging. Furthermore, these mice developed cognitive deficits accompanied by a reduction in spine density and long-term potentiation (LTP) within the hippocampus. At the physiological expression level, mutant FUS is distributed in the nucleus and cytosol without apparent FUS aggregates or nuclear envelope defects. Unbiased transcriptomic analysis revealed a deregulation of genes that cluster in pathways involved in nonsense-mediated decay, protein homeostasis, and mitochondrial functions. Furthermore, the use of in vivo functional imaging demonstrated widespread reduction in cortical volumes but enhanced functional connectivity between hippocampus, basal ganglia and neocortex in R514G-FUS mice. Hence, our findings suggest that disease-linked mutation in FUS may lead to changes in proteostasis and mitochondrial dysfunction that in turn affect brain structure and connectivity resulting in cognitive deficits.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/physiopathology ; Animals ; Brain/metabolism ; Brain/physiopathology ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Functional Neuroimaging ; Humans ; Magnetic Resonance Imaging ; Mice ; Mice, Transgenic ; Mitochondria/metabolism ; Morris Water Maze Test ; Neural Pathways/metabolism ; Neural Pathways/physiopathology ; Nonsense Mediated mRNA Decay/genetics ; Open Field Test ; Proteostasis/genetics ; RNA-Binding Protein FUS/genetics
    Chemical Substances FUS protein, human ; RNA-Binding Protein FUS
    Language English
    Publishing date 2021-01-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-020-01111-4
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  10. Article ; Online: FUS-mediated dysregulation of Sema5a, an autism-related gene, in FUS mice with hippocampus-dependent cognitive deficits.

    Ho, Wan Yun / Chang, Jer-Cherng / Tyan, Sheue-Houy / Yen, Yi-Chun / Lim, Kenneth / Tan, Bernice Siu Yan / Ong, Jolynn / Tucker-Kellogg, Greg / Wong, Peiyan / Koo, Edward / Ling, Shuo-Chien

    Human molecular genetics

    2019  Volume 28, Issue 22, Page(s) 3777–3791

    Abstract: Pathological fused in sarcoma (FUS) inclusions are found in 10% of patients with frontotemporal dementia and those with amyotrophic lateral sclerosis (ALS) carrying FUS mutations. Current work indicates that FUS mutations may incur gain-of-toxic ... ...

    Abstract Pathological fused in sarcoma (FUS) inclusions are found in 10% of patients with frontotemporal dementia and those with amyotrophic lateral sclerosis (ALS) carrying FUS mutations. Current work indicates that FUS mutations may incur gain-of-toxic functions to drive ALS pathogenesis. However, how FUS dysfunction may affect cognition remains elusive. Using a mouse model expressing wild-type human FUS mimicking the endogenous expression pattern and level within the central nervous system, we found that they developed hippocampus-mediated cognitive deficits accompanied by an age-dependent reduction in spine density and long-term potentiation in their hippocampus. However, there were no apparent FUS aggregates, nuclear envelope defects and cytosolic FUS accumulation. These suggest that these proposed pathogenic mechanisms may not be the underlying causes for the observed cognitive deficits. Unbiased transcriptomic analysis identified expression changes in a small set of genes with preferential expression in the neurons and oligodendrocyte lineage cells. Of these, we focused on Sema5a, a gene involved in axon guidance, spine dynamics, Parkinson's disease and autism spectrum disorders. Critically, FUS binds directly to Sema5a mRNA and regulates Sema5a expression in a FUS-dose-dependent manner. Taken together, our data suggest that FUS-driven Sema5a deregulation may underlie the cognitive deficits in FUS transgenic mice.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Animals ; Cell Line, Tumor ; Cognitive Dysfunction/genetics ; Cognitive Dysfunction/metabolism ; Disease Models, Animal ; Female ; Hippocampus/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Neurons/metabolism ; RNA-Binding Protein FUS/genetics ; RNA-Binding Protein FUS/metabolism ; Semaphorins/genetics ; Semaphorins/metabolism
    Chemical Substances FUS protein, human ; FUS protein, mouse ; RNA-Binding Protein FUS ; SEMA5A protein, human ; Sema5A protein, mouse ; Semaphorins
    Language English
    Publishing date 2019-09-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108742-0
    ISSN 1460-2083 ; 0964-6906
    ISSN (online) 1460-2083
    ISSN 0964-6906
    DOI 10.1093/hmg/ddz217
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