title: Targeting disease through novel pathways of apoptosis and autophagy.
abstract: BACKGROUND
  Apoptosis and autophagy impact cell death in multiple systems of the body. Development of new therapeutic strategies that target these processes must address their complex role during developmental cell growth as well as during the modulation of toxic cellular environments.
  
  
  METHODS
  Novel signaling pathways involving Wnt1-inducible signaling pathway protein 1 (WISP1), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), β-catenin and mammalian target of rapamycin (mTOR) govern apoptotic and autophagic pathways during oxidant stress that affect the course of a broad spectrum of disease entities including Alzheimer's disease, Parkinson's disease, myocardial injury, skeletal system trauma, immune system dysfunction and cancer progression. Implications of potential biological and clinical outcome for these signaling pathways are presented.
  
  
  CONCLUSIONS
  The CCN family member WISP1 and its intimate relationship with canonical and non-canonical wingless signaling pathways of PI3K, Akt1, β-catenin and mTOR offer an exciting approach for governing the pathways of apoptosis and autophagy especially in clinical disorders that are currently without effective treatments. Future studies that can elucidate the intricate role of these cytoprotective pathways during apoptosis and autophagy can further the successful translation and development of these cellular targets into robust and safe clinical therapeutic strategies.
authors.affiliation: New Jersey Health Sciences University, Cancer Institute of New Jersey, Laboratory of Cellular and Molecular Signaling, F 1220, 205 South Orange Avenue, Newark, New Jersey 07101, USA. wntin75@yahoo.com
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maiese
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Yan Chen
authors.initials: YC
authors.lastname: Shang
authors.forename: Shaohui
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism; D004194:Disease; D006801:Humans; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D055511:CCN Intercellular Signaling Proteins; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051176:beta Catenin; C116396:CCN4 protein, human; C546842:MTOR protein, human