Abstract
The neuropeptide, neurotensin, exerts numerous biological functions, including an efficient anti-apoptotic role, both in the central nervous system and in the periphery. This review summarizes studies that clearly evidenced the protective effect of neurotensin through its three known receptors. The pivotal involvement of the neurotensin receptor-3, also called sortilin, in the molecular mechanisms of the anti-apoptotic action of neurotensin has been analyzed in neuronal cell death, in cancer cell growth and in pancreatic beta cell protection. The relationships between the anti-apoptotic role of neurotensin and important physiological and pathological contexts are discussed in this review.
Highlights
The tridecapeptide neurotensin (NT) was isolated from bovine hypothalami on the basis of its ability to induce vasodilatation [1]
NTSR3/sortilin in neuronal cell death was performed in 2004 in an original work showing that both sortilin and p75NTR form a protein complex, which is crucial for the apoptotic effect of the precursor form of NGF on neurons [33]
SR48692 efficiently radiosensitized PC-3M orthotopic human tumor xenografts in mice and significantly reduced tumor burden [46]. These findings offer preclinical proof of concept for targeting the NTSR1 receptor as a strategy to improve efficacy and outcomes of prostate cancer treatments using radiotherapy
Summary
The tridecapeptide neurotensin (NT) was isolated from bovine hypothalami on the basis of its ability to induce vasodilatation [1]. The homeostasis of tissues results from a fine equilibrium between cell differentiation, proliferation and apoptosis Both proliferation and apoptosis display crucial roles in the growth control and development of normal and neoplastic tissues. Apoptosis is regulated by multiple intracellular pro- and anti-apoptotic proteins. Members of the Bcl-2 family are globular proteins structured in Į-helices, which possess at least one Bcl-2 homology (BH) domain. The p53 tumor suppressor, which is another representative of pro-apoptotic proteins, limits cell growth by inducing cell cycle arrest and apoptosis. Since p53 mediates apoptosis through a pathway involving Bax, its activity can be blocked by anti-apoptotic Bcl-2 family members [29]. Numerous studies demonstrated a role of NT in the regulation of apoptosis through the activation of the Bcl-2 family proteins. We will focus on the history of the discovery of the anti- and, with a lesser extent, the pro-apoptotic action of NT both in central and peripheral tissues
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