Nutraceutical and therapeutic potential of Phycocyanobilin for treating Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative condition provoking the loss of cognitive and memory performances. Despite huge efforts to develop effective AD therapies, there is still no cure for this neurological condition. Here, we review the main biological properties of Phycocyanobilin (PCB), accounting for its potential uses against AD. PCB, given individually or released in vivo from C-Phycocyanin (C-PC), acts as a bioactive-molecule-mediating antioxidant, is anti-inflammatory and has immunomodulatory activities. PCB/C-PC are able to scavenge reactive oxygen and nitrogen species, to counteract lipid peroxidation and to inhibit enzymes such as NADPH oxidase and COX-2. In animal models of multiple sclerosis and ischemic stroke, these compounds induce remyelination as demonstrated by electron microscopy and the expression of genes such as Mal up-regulation of and Lingo-1 down-regulation. These treatments also reduce pro-inflammatory cytokines levels and induce immune suppressive genes. PCB/C-PC protects isolated rat brain mitochondria and inactivate microglia, astrocytes and neuronal apoptosis mediators. Such processes are all involved in the pathogenic cascade of AD, and thus PCB may effectively mitigate the injury in this condition. Furthermore, PCB can be administered safely by oral or parenteral routes and therefore, could be commercially offered as a nutraceutical supplement or as a pharmaceutical drug.

Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR.

TIR8, also known as single Ig IL-1R-related molecule (SIGIRR), is a member of the IL-1 receptor family. The present study was designed to investigate the expression and function of TIR8. TIR8 was mainly expressed in mouse and human epithelial tissues such as kidney, lung and gut. Resting and activated T and B lymphocytes and monocytes-macrophages expressed little or no TIR8, with the exception of the mouse GG2EE macrophage line. In the kidney, the organ with highest mRNA levels, TIR8 expression was confined to epithelial cells and, in situ, to tubular epithelium. A variety of signals failed to regulate TIR8 expression, but LPS reduced TIR8 mRNA transcripts. An NF-kB driven reporter system was used to investigate the function of TIR8. TIR8 did not activate NF-kB expression alone or in concert with IL-1R1. In contrast, TIR8 inhibited signaling from the IL-1R complex. Inhibition required the intracellular portion of TIR8 but the extracellular domain was dispensable for blocking activity. Thus, TIR8 is a unique member of the IL-1R family, with a distinct pattern of epithelial expression, including the kidney and mucosae, and an inhibitory function on IL-1 signaling.