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Genetic variation in MME in relation to neprilysin protein and enzyme activity, Aβ levels, and Alzheimer's disease risk

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  • Neprilysin (Nep)
  • Also Known As Membrane Metalloendopeptidase (Mme)
  • Is Considered Amongst The Most Important ß-Amyloid (Aß)-Degrading Enzymes With Regard To Prevention
  • Variation In The Nep Gene (Mme) Has Been Suggested As A Risk Factor For Ad
  • We Conducted A Genetic Association Study Of 7Mme Snps - Rs1836914
  • Rs989692
  • Rs9827586
  • Rs6797911
  • Rs61760379
  • Rs3736187
  • Rs701109 - With Respect To Ad Risk In A Cohort Of 1057 Probable And Confirmed Ad Cases And 424 Age-M
  • Italy And Sweden
  • We Also Examined The Association Of These Mme Snps With Nep Protein Level And Enzyme Activity
  • And On Biochemical Measures Of Aß Accumulation In Frontal Cortex - Levels Of Total Soluble Aß
  • Oligomeric Aß(1-42)
  • And Guanidine-Extractable (Insoluble) Aß - In A Sub-Group Of Ad And Control Cases With Post-Mortem B
  • On Multivariate Logistic Regression Analysis One Of The Mme Variants (Rs6797911) Was Associated With
  • 00052
  • Odds Ratio (O
  • R
  • = 1
  • 40
  • 95% Confidence Interval (1
  • 16-1
  • 70))
  • None Of The Snps Had Any Association With Aß Levels
  • However
  • Rs9827586 Was Significantly Associated With Nep Protein Level (P=0
  • 014) And Enzyme Activity (P=0
  • 006)
  • Association Was Also Found Between Rs701109 And Nep Protein Level (P=0
  • 026) And A Marginally Non-Significant Association Was Found For Rs989692 (P=0
  • 055)
  • These Data Suggest That Mme Variation May Be Associated With Ad Risk But We Have Not Found Evidence
  • Biology


Chapter 2 Androgen Action During Prostate Carcinogenesis Diping Wang and Donald J. Tindall Abstract Androgens are critical for normal prostate development and function, as well as prostate cancer initiation and progression. Androgens function mainly by regulating target gene expression through the androgen receptor (AR). Many studies have shown that androgen-AR signaling exerts actions on key events during prostate carcinogenesis. In this review, androgen action in distinct aspects of prostate carcinogenesis, including (i) cell proliferation, (ii) cell apoptosis, and (iii) prostate cancer metastasis will be discussed. Key words: Androgen receptor, prostate cancer, androgen metabolism, androgen signaling, castration-resistant prostate cancer. 1. Androgen Signaling Androgens are the male sex hormones, which control the differ- entiation and maturation of male reproductive organs, including the prostate gland. Testosterone is the principal androgen in cir- culation and is synthesized by Leydig cells in the testes, under the regulation of luteinizing hormone (LH), which is further regulated by gonadotropin-releasing hormone (GnRH). Adrenal glands also synthesize a small amount of androgens, such as dehy- droepiandrosterone (DHEA) and androstenedione (4-dione) (1). Testosterone enters prostate cells by passive diffusion, where it is converted enzymatically by 5-α reductases to the more potent androgen dihydrotestosterone (DHT) (2). Binding of androgens to the androgen receptor (AR), a ligand-modulated transcrip- tion factor, induces a conformational change in the AR, causing release of heat shock proteins and translocation of the AR to the F. Saatcioglu (ed.), Androgen Action, Methods in Molecular Biology 776, DOI 10.1007/978-1-61779-243-4_2, © Springer Science+Business Media, LLC 2011 25 26 Wang and Tindall nucleus, where it transcriptionally regulates the expression of tar- get genes (3). In addition to the classic genomic effects of sex steroids, accu- mulating

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