Of SMN in mice and men: a therapeutic opportunity

Swoboda, Kathryn J.
August 2011
Journal of Clinical Investigation;Aug2011, Vol. 121 Issue 8, p2978
Academic Journal
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that predominantly affects motor neurons, resulting in progressive muscular atrophy and weakness. SMA arises due to insufficient survival motor neuron (SMN) protein levels as a result of homozygous disruption of the SMN1 gene. SMN upregulation is a promising and potent treatment strategy for this currently incurable condition. In this issue of the JCI, two independent research groups report novel observations in mouse models of severe SMA that provide hope that this approach will afford meaningful benefit to individuals with SMA.


Related Articles

  • Site and mechanism of leptin action in a rodent form of congenital lipodystrophy. Asilmaz, Esra; Cohen, Paul; Miyazaki, Makoto; Dobrzyn, Pawel; Ueki, Kohjiro; Fayzikhodjaeva, Gulnorakhon; Soukas, Alexander A.; Kahn, C. Ronald; Ntambi, James M.; Socci, Nicholas D.; Friedman, Jeffrey M. // Journal of Clinical Investigation;Feb2004, Vol. 113 Issue 3, p414 

    Lipociystroplay is characterized by the complete or partial absence of adipose tissue, insulin resistance, hepatic steatosis, and leptin deficiency. Here, we show that low-dose central leptin corrects the insulin resistance and fatty liver of lipodystrophic aP2-nSREBP-1c mice, while the same...

  • Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. Gunshin, Hiromi; Fujiwara, Yuko; Custodio, Angel O.; DiRenzo, Cristina; Robine, Sylvie; Andrews, Nancy C. // Journal of Clinical Investigation;May2005, Vol. 115 Issue 5, p1258 

    Solute carrier family 11, member 2 (SLC11A2) is the only transmembrane iron transporter known to be involved in cellular iron uptake. It is widely expressed and has been postulated to play important roles in intestinal iron absorption, erythroid iron utilization, hepatic iron accumulation,...

  • Denervation stimulates apoptosis but not Id2 expression in hindlimb muscles of aged rats. Alway, Stephen E; Degens, Hans; Krishnamurthy, Gururaj; Chaudhrai, Archana // Journals of Gerontology Series A: Biological Sciences & Medical ;Aug2003, Vol. 58 Issue 8, p687 

    Inhibitors of differentiation (Id) proteins are repressors of myogenic regulatory factors and have been implicated in apoptosis and muscle atrophy during aging. Indeed, we have previously found that Id levels are elevated in muscles from old rodents, possibly as a consequence of loss of...

  • FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. Kamagate, Adama; Shen Qu; Perdomo, German; Dongming Su; Dae Hyun Kim; Slusher, Sandra; Meseck, Marcia; Dong, H. Henry; Qu, Shen; Su, Dongming; Kim, Dae Hyun // Journal of Clinical Investigation;Jun2008, Vol. 118 Issue 6, p2347 

    Excessive production of triglyceride-rich VLDL is attributable to hypertriglyceridemia. VLDL production is facilitated by microsomal triglyceride transfer protein (MTP) in a rate-limiting step that is regulated by insulin. To characterize the underlying mechanism, we studied hepatic MTP...

  • RhoA protects the mouse heart against ischemia/reperfusion injury. Sunny Yang Xiang; Vanhoutte, Davy; Del Re, Dominic P.; Purcell, Nicole H.; Haiyun Ling; Banerjee, Indroneal; Bossuyt, Julie; Lang, Richard A.; Yi Zheng; Matkovich, Scot J.; Miyamoto, Shigeki; Molkentin, Jeffery D.; Dorn II, Gerald W.; Brown, Joan Heller; Xiang, Sunny Yang; Ling, Haiyun; Zheng, Yi; Dorn, Gerald W 2nd // Journal of Clinical Investigation;Aug2011, Vol. 121 Issue 8, p3269 

    The small GTPase RhoA serves as a nodal point for signaling through hormones and mechanical stretch. However, the role of RhoA signaling in cardiac pathophysiology is poorly understood. To address this issue, we generated mice with cardiomyocyte-specific conditional expression of low levels of...

  • Mitochondria. Chinnery P F; Schon E A; Chinnery, P F; Schon, E A // Journal of Neurology, Neurosurgery & Psychiatry;Sep2003, Vol. 74 Issue 9, p1188 

    Following the discovery in the early 1960s that mitochondria contain their own DNA (mtDNA), there were two major advances, both in the 1980s: the human mtDNA sequence was published in 1981, and in 1988 the first pathogenic mtDNA mutations were identified. The floodgates were opened, and the...

  • The TEL-AML1 leukemia fusion gene dysregulates the TGF-beta pathway in early B lineage progenitor cells. Ford, Anthony M.; Palmi, Chiara; Bueno, Clara; Dengli Hong; Cardus, Penny; Knight, Deborah; Cazzaniga, Giovanni; Enver, Tariq; Greaves, Mel; Hong, Dengli // Journal of Clinical Investigation;Apr2009, Vol. 119 Issue 4, p826 

    Chromosome translocation to generate the TEL-AML1 (also known as ETV6-RUNX1) chimeric fusion gene is a frequent and early or initiating event in childhood acute lymphoblastic leukemia (ALL). Our starting hypothesis was that the TEL-AML1 protein generates and maintains preleukemic clones and that...

  • Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans. Banks, Alexander S.; Jianze Li; McKeag, Lisa; Hribal, Marta L.; Kashiwada, Masaki; Accili, Domenico; Rothman, Paul B.; Li, Jianze // Journal of Clinical Investigation;Sep2005, Vol. 115 Issue 9, p2462 

    NIDDM is characterized by progressive insulin resistance and the failure of insulin-producing pancreatic beta cells to compensate for this resistance. Hyperinsulinemia, inflammation, and prolonged activation of the insulin receptor (INSR) have been shown to induce insulin resistance by...

  • PHF6 mutations in adult acute myeloid leukemia. Van Vlierberghe, P.; Patel, J.; Abdel-Wahab, O.; Lobry, C.; Hedvat, C. V.; Balbin, M.; Nicolas, C.; Payer, A. R.; Fernandez, H. F.; Tallman, M. S.; Paietta, E.; Melnick, A.; Vandenberghe, P.; Speleman, F.; Aifantis, I.; Cools, J.; Levine, R.; Ferrando, A. // Leukemia (08876924);Jan2011, Vol. 25 Issue 1, p130 

    Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics