2021
DOI: 10.1523/eneuro.0350-21.2021
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Knock-Down of Heterogeneous Nuclear Ribonucleoprotein A1 Results in Neurite Damage, Altered Stress Granule Biology, and Cellular Toxicity in Differentiated Neuronal Cells

Abstract: Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA binding protein (RBP) that is localized within neurons and plays crucial roles in RNA metabolism. Its importance in neuronal functioning is underscored from the study of its pathogenic features in many neurodegenerative diseases where neuronal hnRNP A1 is mislocalized from the nucleus to the cytoplasm resulting in loss of hnRNP A1 function. Here, we model hnRNP A1 loss-of-function by siRNA mediated knockdown in differentiated Neuro-2a cells. Throu… Show more

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Cited by 11 publications
(16 citation statements)
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“…Collectively, our data highlight an important role for hnRNP A1 in proper OL functioning and survival and suggest a potential mechanism of OL damage and death in MS that involves hnRNP A1 dysfunction. This adds to our ongoing work (Anees et al, 2021; Li et al, 2021; Libner et al, 2020; Salapa et al, 2018; Salapa, Hutchinson, et al, 2020; Salapa, Libner, & Levin, 2020) that hnRNP A1 dysfunction in neurons contributes to neurodegeneration in MS and its models. Along with the data presented here, in which we show that hnRNP A1 dysfunction in OLs leads to OL death, damage and subsequent demyelination, suggest that together, hnRNP A1 dysfunction in both OLs and neurons combine to contribute to central nervous system damage and subsequent disability in MS. Future studies should expand on the role hnRNP A1 dysfunction may play in the ability of OLs to properly maintain or produce new myelin.…”
Section: Discussionmentioning
confidence: 69%
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“…Collectively, our data highlight an important role for hnRNP A1 in proper OL functioning and survival and suggest a potential mechanism of OL damage and death in MS that involves hnRNP A1 dysfunction. This adds to our ongoing work (Anees et al, 2021; Li et al, 2021; Libner et al, 2020; Salapa et al, 2018; Salapa, Hutchinson, et al, 2020; Salapa, Libner, & Levin, 2020) that hnRNP A1 dysfunction in neurons contributes to neurodegeneration in MS and its models. Along with the data presented here, in which we show that hnRNP A1 dysfunction in OLs leads to OL death, damage and subsequent demyelination, suggest that together, hnRNP A1 dysfunction in both OLs and neurons combine to contribute to central nervous system damage and subsequent disability in MS. Future studies should expand on the role hnRNP A1 dysfunction may play in the ability of OLs to properly maintain or produce new myelin.…”
Section: Discussionmentioning
confidence: 69%
“…Collectively, our data highlight an important role for hnRNP A1 in proper OL functioning and survival and suggest a potential mechanism of OL damage and death in MS that involves hnRNP A1 dysfunction. This adds to our ongoing work (Anees et al, 2021;Li et al, 2021;Libner et al, 2020;Salapa et al, 2018;Salapa, Hutchinson, et al, 2020;) that hnRNP A1 dysfunction in neurons contributes to neurodegeneration in MS and its models.…”
Section: Hnrnp A1 Dysfunction Disrupts Ol Morphology Viability and Ac...mentioning
confidence: 63%
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“…HNRNPA1 is involved in several neuronal processes including the regulation of neuron morphology, viability, and stress granule formation (Low et al, 2021). Thus, dysfunction of HNRNPA1 induces neuronal deficits and its knock down was reported to reduce neurite outgrowth, increase in cell toxicity, and change in stress granule formation (Anees et al, 2021). Supporting a role of HNRNPA1 in neuronal processes, Lee and colleagues identified nine single‐nucleotide polymorphisms (SNPs) in MS patients contributing to HNRNPA1 dysfunction.…”
Section: Role Of Rbps In Multiple Sclerosismentioning
confidence: 99%