Targeting disease through novel pathways of apoptosis and autophagy.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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: Kenneth Maiese, Zhao Zhong Chong, Yan Chen Shang, Shaohui Wang
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 16 Issue 12 Pg. 1203-14 (Dec 2012) ISSN: 1744-7631 [Electronic] England
• PMID: 22924465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• CCN Intercellular Signaling Proteins
• CCN4 protein, human
• Proto-Oncogene Proteins
• beta Catenin
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Apoptosis (physiology)
• Autophagy (physiology)
• CCN Intercellular Signaling Proteins (metabolism)
• Disease
• Humans
• Oxidative Stress
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• TOR Serine-Threonine Kinases (metabolism)
• beta Catenin (metabolism)