In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.

Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathology of Alzheimer's disease (AD) and Parkinson's disease (PD). This review article presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated protection and the signal transduction involved in this mechanism. The data is based mainly on our studies using rat-cultured primary neurons. Nicotine-induced protection was blocked by an alpha7 nAChR antagonist, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and an Src inhibitor. Levels of phosphorylated Akt, an effector of PI3K, Bcl-2 and Bcl-x were increased by nicotine administration. From these experimental data, our hypothesis for the mechanism of nAChR-mediated survival signal transduction is that the alpha7 nAChR stimulates the Src family, which activates PI3K to phosphorylate Akt, which subsequently transmits the signal to up-regulate Bcl-2 and Bcl-x. Up-regulation of Bcl-2 and Bcl-x could prevent cells from neuronal death induced by beta-amyloid (Abeta), glutamate and rotenone. These findings suggest that protective therapy with nAChR stimulation could delay the progress of neurodegenerative diseases such as AD and PD.
Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models.

Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53R172P, which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4/p53R172P mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70/ p53R172P mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4/p53R172P phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70/p53R172P colonic epithelial cells show nuclear stabilization of -catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70/ mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.
A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining

Signals released by the Spemann organizer of the amphibian gastrula can directly induce neural tissue from ectoderm and can dorsalize ventral mesoderm to form muscle. The secreted polypeptide noggin mimics these activities and is expressed at the appropriate time and place to participate in the organizer signal. Neural induction and mesoderm dorsalization are antagonized by bone morphogenetic proteins (BMPs), which induce epidermis and ventral mesoderm instead. Here we report that noggin protein binds BMP4 with high affinity and can abolish BMP4 activity by blocking binding to cognate cell-surface receptors. These data suggest that noggin secreted by the organizer patterns the embryo by interrupting BMP signaling.
The Spemann Organizer Signal noggin Binds and Inactivates Bone Morphogenetic Protein 4