Перегляд вихідного коду сторінки A Neutral Review Of DZNeP

, 1997). The observation that Gem levels are deficient in ALS patient fibroblasts raises the interesting possibility that Gem levels can be used as a rapid diagnostic marker. For example, Gem levels may be potentially useful for subtyping FUS and TDP-43 forms of the disease. However, further ALS patient fibroblasts containing FUS, TDP-43, or other mutations must [http://en.wikipedia.org/wiki/Carboplatin Carboplatin] be analyzed in future work to determine the generality of the Gem phenotype. The observation that both SMA and ALS (at least some subtypes) have a Gem phenotype also raises the possibility that drug candidates identified for SMA may be efficacious for ALS. Our observation that overexpression of SMN rescues Gem levels in FUS knockdown cells, and recent work showing that overexpression of SMN delays disease onset in an SOD1 mouse ALS model (Kariya et?al., 2012) provide a rationale for testing SMA therapeutics that both increase Gem levels and rescue motor neuron defects. The multiple links identified among FUS, TDP-43, SOD1, the SMN complex, U1 snRNP, and Gems provide strong support for the view that defects in RNA metabolism are involved in the pathogenesis of motor neuron disease. In future work, it will be important to assess components of these RNA complexes for mutations that may be candidates for ALS or SMA susceptibility genes or risk factors. His-SMN and His-LC3 proteins were obtained from Enzo Life Sciences. The SMN-GFP expression plasmid was obtained from Origene. Rabbit polyclonal antibodies were raised against GST-FUS (Covance). We obtained antibodies to SMN (2B1), Sm (Y12), and Gemin3 (12H12) [http://www.selleckchem.com/products/3-deazaneplanocin-a-dznep.html DZNeP price] from Abcam; U1-70K (9C4.1) and Gemin2 (2E17) from Millipore; TDP-43 from Proteintech; U1A (BJ-7), HA, Tubulin, Gemin4 (E-8), and Gemin6 (20H8) from Santa Cruz; and FLAG from Sigma. SAP130 and HA were used as negative controls for polyclonal and monoclonal antibodies, respectively. IP and GST pulldowns were performed as previously described (Das et?al., 2007). Gel samples were trypsin digested and peptides were analyzed by liquid chromatography�Ctandem MS (LC-MS/MS). FUS and control immunoprecipitates were TCA precipitated and analyzed by LC-MS/MS. Keratin and likely contaminants (e.g., desmoplakin, actin, tubulin, myosin, and translation [http://www.selleckchem.com/products/BI6727-Volasertib.html http://www.selleckchem.com/products/BI6727-Volasertib.html] proteins) were not included in Table S1. Proteins found in the negative control immunoprecipitate were not included in Table S1 if the total amount of peptides was