ADAM9 peptide

ADAM9 (A Disintegrin And Metalloproteinase 9) is a member of the ADAM protein family which contains a disintegrin domain. This protein family plays key roles in many physiological processes, including fertilization, migration, and cell survival. The ADAM proteins have also been implicated in various diseases, including cancer. Specifically, ADAM9 has been suggested to be involved in metastasis. To address this question, we generated ADAM9 knockdown clones of MDA-MB-231 breast tumor cells using silencing RNAs that were tested for cell adhesion, proliferation, migration and invasion assays. In RNAi-mediated ADAM9 silenced MDA-MB-231 cells, the expression of ADAM9 was lower from the third to the sixth day after silencing and inhibited tumor cell invasion in matrigel by approximately 72% when compared to control cells, without affecting cell adhesion, proliferation or migration. In conclusion, the generation of MDA-MB-231 knockdown clones lacking ADAM9 expression inhibited tumor cell invasion in vitro, suggesting that ADAM9 is an important molecule in the processes of invasion and metastasis. (C) 2013 Elsevier Masson SAS. All rights reserved.

Amyloid beta (A beta) plaques are pathological hallmarks of neurodegenerative Alzheimer's disease (AD) that is predominantly characterized by clinical symptoms of dementia. Therapies targeting A beta are essential for preventing and treating AD. This review focuses on the non-amyloidogenic pathways that prevent the generation of A beta peptide and thereby plaque formation in AD. An a-secretase-dependent cleavage of Amyloid Precursor Protein (APP) precludes the amyloidogenic pathway of A beta generation. This non-amyloidogenic a-secretase activation thereby secretes sAPPa with prominent neurotrophic and memory-enhancing properties. Several "A Disintegrin and Metalloprotease" (ADAM) proteins, specifically ADAM17, ADAM10 and ADAM9, comprise active members of this a-secretase family. It is conventionally accepted that whereas ADAM10 executes constitutive APP cleavage, ADAM17 and ADAM9 are dedicated towards the regulated processing. Therefore, promoting a-secretase activity offers thorough neuroprotection against AD, and emerges as a pertinent strategy in attenuating A beta. We discuss signaling pathways, particularly those mediated by protein kinase C and phorbol esters, that enhance ADAM functioning and sAPPa release. We also elaborate upon the associated M1 and M3-muscarinic acetylcholine receptors, ERK-MAP kinase, tyrosine kinase and calcium signaling pathways. Clinical studies suggest that regulated hormone and cholesterol levels are essential for restricting neurodegeneration, and here we illustrate the role of estrogen and testosterone and that of cholesterol-attenuating statins in generating sAPPa. We also emphasize the need for novel ADAM activators that may be screened for targeting the interleukin-1-responsive mRNA 5'-untranslated region of APP. This review offers an in-depth insight into pathways, strategies and probable therapies restricting AD pathology via its non-amyloidogenic route.