Neuronal survival

The first report of the action of a chemokine on neurons was published in 1993. The study demonstrated that IL-8 could increase the survival of cultured neurons (Araujo and Cotman, 1993). However, as can be appreciated from its name, IL-8 was not known to be a chemokine at that time and was instead classed as an interleukin. Indeed, the expression of chemokine receptors by neurons was not generally appreciated until around 1997/1998 when several reports suggested this. These reports included observations of the expression of chemokine receptors by neuronal cell lines (Hesselgesser et al. 1997), primary cultures of neurons (Meucci et al. 1998 Ohtani et al. 1998), and in brain sections from HlV-1, Alzheimer s disease, and other patients (Horuk et al. 1997 Westmoreland et al. 1998 Xia et al. 1997). Furthermore, data were obtained, suggesting functions for chemokine signaling in the development of the nervous system (Zou et al. 1998) as well as in neuronal survival and communication (Giovannelli et al. 1998 Meucci et al. 1998). 

CXCR4/CXCL12 signaling is also involved in neuronal survival in health and disease, which is discussed below particularly in the context of neuroAlDS. 

Role of Cell Cycle Proteins in Chemokine Receptor-Mediated Neuronal Survival... 

Cyclin-dependent kinase 5 (cdk5) is a nonconventional cdk which plays important roles in the neuronal survival. Supernatants from HIV-infected macrophages... 

Meucci O, Eatatis A, Simen AA, Miller RJ (2000) Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival. Proc Natl Acad Sci U S A 97 8075-8080 Miller RJ, Tran PB (2005) Chemokinetics. Neuron 47 621-623... 

Unfortunately transplants require 6-7 foetal brains to obtain enough transplantable material for one patient, which itself raises ethical considerations, and as the tissue cannot diffuse its influence is restricted, even with multiple injection sites, and only a fraction (approx. 20%) of the neurons survive. Also without knowledge of the cause of PD the transplant could meet the same fate as the original neurons. The concept, however, demands perseverance and a number of variants are being tried. 

Corotto R, Henegar J. and Maruniak J. (1994). Odor deprivation leads to reduced neurogenesis and reduced neuronal survival in the olfactory bulb of the adult mouse. Neuroscience 61, 739-744. 

Neuronal survival and differentiation are regulated by many factors including neurotrophins and the Trk family of RPTKs. The prototype neurotrophin, nerve growth factor (NGF), promotes the survival of neurons during a period of programmed cell death in embryonic and early postnatal developmental stages. It is a target-derived neurotrophic factor that modulates the functions of the... 

Davies, A. M. Regulation of neuronal survival and death by extracellular signals during development. EMBO J. 22 2537-2545, 2003. 

Brunet, A, Datta, S. R. and Greenberg, M. E. Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11 297-305,2001. 

Edsall, L.C., Pirianov, G.G. and Spiegel, S., 1997, Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation, J. Neurosci. 17 6952-6960. 

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