Prof. Reuven Stein

מחלקה לנוירוביולוגיה סגל אקדמי בכיר
Prof. Reuven Stein
Phone: 03-6408608
Fax: 03-6407643
Office: Sherman - Life Sciences, 724

Research Interests

The research in our laboratory focuses on three main topics.

  1. Neurodegeneration/neuroinflammation and their relationship to apoptosis:  Our aim is to study neurodegeneration (acute and chronic) in relation to cell death and survival and the interplay between these processes to neuroinflammation. In previous studies we showed that neuronal activity can promote the survival of neuronal-like cells under stressed condition and studied the association of the Alzheimer's disease-associated proteins, the presenilins, with apoptosis.
  2. The mechanism of action of pro-apoptotic proteins of the Bcl-2 family:  The Bcl-2 family of proteins contains both anti- and pro-apoptotic members. The bcl-x gene encodes a 233-amino-acid protein containing four BH domains and a transmembrane region (Bcl-xL), Bcl-xS; however, as a result of alternative splicing, lacks an internal 63-amino-acid segment that contains the conserved BH1 and BH2 domains. It therefore contains only the BH3 and BH4 domains and the transmembrane region. Our studies showed that Bcl-xS induces apoptosis by mechanism which resembles the action of BH3-only proteins, i.e., it activates Bax and Bak and leads to the perforation of the mitochondria and to the induction of the apoptosome pathway. However, Bcl-xS has also some unique features such as an ability to form homodimers and the unique requirement of Bak for mediating its apoptotic effects in mouse embryonic fibroblasts (MEFs).
  3. The mechanism whereby the tumor suppressor neurofibromin regulates apoptosis and brain deficits:  Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras- GTPase-activating protein (GAP) activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1.

 

For a more detailed research description 

 

Recent Publications

Lindenboim, L., R. Haviv, and R. Stein. 1995. Inhibition of drug-induced apoptosis by survival factors in PC12 cells. J Neurochem 64: 1054-1063.

 

Pinkas-Kramarski, R., R. Stein, L. Lindenboim, and M. Sokolovsky. 1992. Growth factor-like effects mediated by muscarinic receptors in PC12M1 cells. J Neurochem 59: 2158-2166.

 

Leloup, C., D. M. Michaelson, A. Fisher, T. Hartmann, K. Beyreuther, and R. Stein. 2000. M1 muscarinic receptors block caspase activation by phosphoinositide 3-kinase- and MAPK/ERK-independent pathways. Cell Death Differ 7: 825-833.

 

Gamliel, A., C. Teicher, T. Hartmann, K. Beyreuther, and R. Stein. 2003. Overexpression of wild-type presenilin 2 or its familial Alzheimer's disease-associated mutant does not induce or increase susceptibility to apoptosis in different cell lines. Neuroscience 117: 19-28.

 

Gamliel, A., C. Teicher, D. M. Michaelson, L. Pradier, T. Hartmann, K. Beyreuther, and R. Stein. 2002. Increased expression of presenilin 2 inhibits protein synthesis. Mol Cell Neurosci 19: 111-124.

 

Mayo, L., and R. Stein. 2007. Characterization of LPS and interferon-gamma triggered activation-induced cell death in N9 and primary microglial cells: induction of the mitochondrial gateway by nitric oxide. Cell Death Differ 14: 183-186.

 

Nadler, Y., A. Alexandrovich, N. Grigoriadis, T. Hartmann, K. S. Rao, E. Shohami, and R. Stein. 2008. Increased expression of the gamma-secretase components presenilin-1 and nicastrin in activated astrocytes and microglia following traumatic brain injury. Glia 56: 552-567.

 

Mayo L, Jacob-Hirsch J, Amariglio N, Rechavi G, Moutin MJ Lund FE and R. Stein. Dual role of CD38 in microglial activation and activation induced cell death. J. Immunol.181: 92-103.

 

Lindenboim, L., C. Borner, and R. Stein. 2001. Bcl-x(S) can form homodimers and heterodimers and its apoptotic activity requires localization of Bcl-x(S) to the mitochondria and its BH3 and loop domains.Cell Death Differ 8: 933-942.

 

Lindenboim, L., S. Kringel, T. Braun, C. Borner, and R. Stein. 2005. Bak but not Bax is essential for Bcl-xS-induced apoptosis. Cell Death Differ 12: 713-723.

 

Lindenboim, L., S. Schlipf, T. Kaufmann, C. Borner, and R. Stein. 2004. Bcl-x(S) induces an NGF-inhibitable cytochrome c release. Exp Cell Res 297: 392-403.

 

Lindenboim, L., J. Yuan, and R. Stein. 2000. Bcl-xS and Bax induce different apoptotic pathways in PC12 cells. Oncogene 19: 1783-1793.

 

Braun, T., S. Dar, D. Vorobiov, L. Lindenboim, N. Dascal, and R. Stein. 2003. Expression of Bcl-x(S) in Xenopus oocytes induces BH3-dependent and caspase-dependent cytochrome c release and apoptosis. Mol Cancer Res 1: 186-194.

 

Shapira, S., B. Barkan, E. Friedman, Y. Kloog, and R. Stein. 2007. The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways. Cell Death Differ 14: 895-906.

 

Tel Aviv University, P.O. Box 39040, Tel Aviv 6997801, Israel
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