Immunity to self and self-maintenance: what can tumor immunology teach us about ALS and Alzheimer's disease?

Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Trends in Pharmacological Sciences (Impact Factor: 9.99). 07/2008; 29(6):287-93. DOI: 10.1016/
Source: PubMed

ABSTRACT Mounting evidence from the last decade has shown that the immune system not only fights pathogens but also protects the body against cancer. More recently, immune surveillance has been shown to be important for maintaining the functional integrity of the central nervous system. The immune system, however, does not always prevail; tumors do grow and eventually kill their host, and devastating neurodegenerative conditions do develop. Neurodegenerative diseases, like tumors, lie dormant long before clinical symptoms appear. We propose that at this dormant stage, an ongoing competition between the local disease-causing factors and the immune system's attempts to contain them takes place. Onset of clinical symptoms occurs after disease-causing factors escape immune surveillance. Identifying the immune escape mechanisms and circumventing them soon after the emergence of clinical symptoms could lead to the development of novel therapeutic intervention for some of the most devastating neurodegenerative disorders.

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    • "In addition to activation along an inflammatory pathway, microglia can also become activated along several other pathways as well (Michelucci et al., 2009; Derecki et al., 2011). Microglia can assume a form of activation through which they maintain the health of neurons (Butovsky et al., 2006; Schwartz and Ziv, 2008b; Ekdahl et al., 2009; Kosloski et al., 2010). When in the growth promoting mode, microglia release Insulin-like growth factor-1 (IGF-1; Butovsky et al., 2005; Ekdahl et al., 2009; Kosloski et al., 2010; Schwartz and Shechter, 2010a; Ron-Harel et al., 2011). "
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    Frontiers in Psychology 08/2012; 3:297. DOI:10.3389/fpsyg.2012.00297 · 2.80 Impact Factor
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    • "Moreover, the spontaneous recovery from CNS insults and the ability to cope with mental stress was shown to be T celldependent (Cohen et al., 2006; Kipnis et al., 2004b; Lewitus and Schwartz, 2009; Moalem et al., 1999; Yoles et al., 2001). Since basal immune maintenance is not sufficient to counteract the forces that drive neurotoxicity, boosting the protective T-cell response can be accomplished either by active immunization with the relevant self CNS antigens or via modulation of the naturally occurring T regulatory cells (Tregs), which constitutively suppress potential anti-self helper (CD4 + ) T cells (Kipnis et al., 2002; Schwartz and Ziv, 2008). One way to achieve this aim is by administration of poly-YE, a high-molecular-weight copolymer (22–45 kDa) of glutamate and tyrosine with immunomodulatory properties (Cady et al., 2000; Vidovic and Matzinger, 1988), which is able to down-regulate the suppressive properties of Tregs (Ziv et al., 2007). "
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    • "The peroxisome proliferatoractivated receptor gamma (PPARγ) agonist, pioglitazone, a thiazolidinedione anti-diabetic agent, with reported anti-inflammatory properties, improved muscle strength, body weight and survival as well as demonstrated delayed disease onset when compared to nontreated SOD1- G93A mice (Schutz, et al., 2005). Copaxone, an immune modulatory drug has also been shown to affect survival; however, later results have not been confirmed (Gordon, et al., 2006, Haenggeli, et al., 2007, Schwartz and Ziv, 2008). "
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