Advances in Down Syndrome Research by Y. Kazuki, T. C. Schulz, T. Shinohara, M. Kadota (auth.),

By Y. Kazuki, T. C. Schulz, T. Shinohara, M. Kadota (auth.), Prof. Dr. G. Lubec (eds.)

"Advances in Down Syndrome study” represents up to date learn in different parts of Down Syndrome (DS). a brand new promising animal version of DS is suggested and this opens new possibilities to review pathomechanisms and pharmacological techniques because it is greater than tough to hold out reviews in people and the medical beneficial properties are hugely variable. when it comes to biology, mobilephone cycle and stem telephone experiences and when it comes to biochemistry, relevance of experiences on a particular protein kinase, channels, transporters, superoxide dismutase, antioxidant approach, chromosome meeting issue and different very important organic constructions are supplied. And back, the gene dosage speculation is addressed and even supposing the majority of chromosome 21 gene items is unchanged in fetal DS mind, a couple of particular chromosome 21 encoded buildings together with transcription elements are certainly overexpressed even if findings in fetal DS are assorted from these in grownup DS mind whilst Alzheimer-like neuropathology supervenes.

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Groner (Department of Molecular Genetics, The Weizmann Institue of Science, Israel) for the antibody against RUNXl. We are highly indebted to the Red Bull Company, Salzburg, for generous financial support. References Asou N (2003) The role of a Runt domain transcription factor AMLl/RUNX1 in leukemogenesis and its clinical implications. Crit Rev Oncol Rematol 45: 129-150 Aberrant protein expression of transcription factors BACH1 and ERG 47 Aziz-Aloya RB, Levanon D, Karn H, Kidron D, Goldenberg D, Lotem J, Polak-Chaklon S, Groner Y (1998) Expression of AMLl-d, a short human AMLl isoform, in embryonic stem cells suppresses in vivo tumor growth and differentiation.

Protein lysates were prepared from cerebrums or hippocampi dissected from five Ts65Dn and five normal controls, of approximately 4-6 months of age. a Western blots were probed with antibodies recognizing only the phosphorylated forms of Erkl and Erk2. WI-W5, wild type (normal) mice; Tl-T5, trisomic mice. b,c Levels of pErkl and pErk2 in the Ts65Dn were compared to the corresponding average levels in normal mice. 0001) by the t-test. Data are from 3-5 replicates Predicting pathway perturbations in Down syndrome 33 i) While the analysis shows that chromosome 21 contains genes predicted to function in a very broad range of cellular processes, only 94 and 71 of these are trisomic in the mouse chromosome 16 segmental trisomies, Ts65Dn and Ts1Cje.

DSCR1 is induced by calcineurin, implying a negative feedback mechanism (Yang et aL, 2000), and by Ca2+, by H 20 2, and by the Alzheimers amyloid precursor protein (APP) A~42 peptide (reviewed in Rothermel et aL, 2003). SOD1, Superoxide Dismutase, produces H 20 2; its increased production in DS is believed to contribute to the observed increased levels of oxidative damage which may also serve to increase levels of DSCRl. The transcription factor ETS2 and the APP cleavage protein, BACE2, are also induced by H 20 2 (Tamagno et aL, 2002; Sanji et aL, 2001).

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