2019
DOI: 10.1016/j.stem.2019.04.016
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Mir-17∼92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration

Abstract: Highlights d A mouse ESC-based double reporter system recapitulates motor neuron subtype degeneration d Mir-1792/nuclear PTEN pathway underlies vulnerability of LMC-MNs in SOD1 G93A mice d Mir-1792 overexpression prevents human SOD1 +/L144F MN degeneration d AAV9-mediated mir-1792 delivery in adult SOD1 G93A mice prolongs lifespan

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Cited by 40 publications
(47 citation statements)
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“…All spinal MNs are generated from pMNs, and pMNs are established upon co-expression of Olig2, Nkx6.1 and Nkx6.2 under conditions of high Shh levels [2,105,132,162]. Although a series of miRNAs have been shown to facilitate patterning of the neuronal progenitors in the spinal cord and controlling of MN differentiation [24,25,27,74,141,142], the roles of lncRNAs during MN development are just beginning to emerge. In Table 1, we summarize the importance of lncRNAs for the regulation of transcription factors in MN contexts.…”
Section: Role Of Lncrnas In Regulating Neural Progenitorsmentioning
confidence: 99%
See 1 more Smart Citation
“…All spinal MNs are generated from pMNs, and pMNs are established upon co-expression of Olig2, Nkx6.1 and Nkx6.2 under conditions of high Shh levels [2,105,132,162]. Although a series of miRNAs have been shown to facilitate patterning of the neuronal progenitors in the spinal cord and controlling of MN differentiation [24,25,27,74,141,142], the roles of lncRNAs during MN development are just beginning to emerge. In Table 1, we summarize the importance of lncRNAs for the regulation of transcription factors in MN contexts.…”
Section: Role Of Lncrnas In Regulating Neural Progenitorsmentioning
confidence: 99%
“…Consequently, miRNA production is compromised, with several miRNAs (i.e. miR-17~92 and miR-218) perhaps directly participating in ALS disease onset and progression [56,142]. Mislocalization of ALS-related proteins such as FUS and TDP-43 in the cytosol rather than nucleus of MNs has been observed in ALS patients, but the mechanism remains unclear [125,146].…”
Section: Lncrnas In Liquid-liquid Phase Separation (Llps) and Motor Nmentioning
confidence: 99%
“…A calcium-binding ER chaperone calreticulin is reduced in SMN vulnerable to ALS [45], and further reduction of calreticulin levels by breeding hSOD1 G93A mice with hemizygous calreticulin mutant mice accelerated disease onset and progression [40]. Expression of mir 17~92 was reduced in vulnerable SMN prior to disease onset in hSOD1 G93A mice, and gene therapy using AAV-mediated intrathecal mir 17~92 delivery improved motor function and survival [46]. Misfolded SOD1 protein binds to the cytoplasmic surface of mitochondria in SMN, and disrupts the normal mitochondria size, shape, and distribution [47].…”
Section: Discussionmentioning
confidence: 99%
“…This cluster targets an E3 ubiguitin ligase to regulate monoubiquitination of PTEN, which determines the subcellular location of the protein. By this mechanism, miR17-92 is able to regulate motor neuron vulnerability in ALS [145,146]. In another example, treatments to suppress miR-155, which is upregulated in ALS model rodents and patient spinal cord, improve survival in SOD1 G93A rodent models mainly by blocking miR-155 function in microglia, astrocytes and neurons [22,147].…”
Section: Ncrnas In Other Mechanisms Of Ad Pathogenesismentioning
confidence: 99%