HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 26, 24941-24947, July 1, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/26/24941    most recent M413495200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lesné, S. Articles by Buisson, A. Search for Related Content PubMed PubMed Citation Articles by Lesné, S. Articles by Buisson, A. Social Bookmarking                      What's this?

Akt-dependent Expression of NAIP-1 Protects Neurons against Amyloid- Toxicity^*

Sylvain Lesné, Cecilia Gabriel, Deirdre A. Nelson¶, Eileen White¶, Eric T. MacKenzie, Denis Vivien, and Alain Buisson||

From the UMR CNRS 6185, Université de Caen, Bd. H. Becquerel BP5229, 14074 Caen, France and ^¶Howard Hughes Medical Institute, Rutgers University, Piscataway, New Jersey 08854

Neurotrophins are a family of growth factors that attenuate several forms of pathological neuronal cell death and may represent a putative therapeutic approach to neurodegenerative diseases. In Alzheimer disease, amyloid- (A) is thought to play a central role in the neuronal death occurring in brains of patients. In the present study, we evaluate the ability of neurotrophin-3 (NT-3) to protect neurons against the toxicity induced by aggregated A. We showed that in primary cultures of cortical neurons, NT-3 reduces A-induced apoptosis by limiting caspase-8, caspase-9, and caspase-3 cleavage. This neuroprotective effect of NT-3 was concomitant to an increased level of Akt phosphorylation and was abolished by an inhibitor of the phosphatidylinositol-3 kinase (PI-3K), LY294002. In parallel, NT-3 treatment reduced A induced caspase-3 processing to control levels. In an attempt to link PI-3K/Akt to caspase inhibition, we evaluated the influence of the PI-3K/Akt axis on the expression of a member of the inhibitors of apoptosis proteins (IAPs), the neuronal apoptosis inhibitory protein-1. We demonstrated that NT-3 induces an up-regulation of neuronal apoptosis inhibitory protein-1 expression in neurons that promotes the inhibition of A-induced neuronal apoptosis. Together, these findings demonstrate that NT-3 signaling counters A-dependent neuronal cell death and may represent an innovative therapeutic intervention to limit neuronal death in Alzheimer disease.

Received for publication, December 1, 2004 , and in revised form, February 22, 2005.

^* This work was supported by grants from the Regional Council of Lower Normandy (to S. L.) and Foundation for Medical Research (to C. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: University of Minnesota, Dept. of Neurology, 420 Delaware St. SE, MMC295, Minneapolis, MN 55455.

^|| To whom correspondence should be addressed. Tel.: 33-2-31-56-60-39; Fax: 33-2-31-56-61-99; E-mail: a.buisson{at}neuro.unicaen.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Zhang, B. Marshall, and S. S. Atherton Murine Cytomegalovirus Infection and Apoptosis in Organotypic Retinal Cultures Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 295 - 303. [Abstract] [Full Text] [PDF]

				Y. Yin, W.-W. Huang, C. Lin, H. Chen, A. MacKenzie, and L. Ma Estrogen Suppresses Uterine Epithelial Apoptosis by Inducing Birc1 Expression Mol. Endocrinol., January 1, 2008; 22(1): 113 - 125. [Abstract] [Full Text] [PDF]

				R. R. Romito-DiGiacomo, H. Menegay, S. A. Cicero, and K. Herrup Effects of Alzheimer's Disease on Different Cortical Layers: The Role of Intrinsic Differences in A{beta} Susceptibility J. Neurosci., August 8, 2007; 27(32): 8496 - 8504. [Abstract] [Full Text] [PDF]