protective role in transthyretin deposition in ATTR, although significantly lower levels of circulating clusterin were associated with UPF 1069 supplier amyloid deposition in the heart in ATTR, is what appears to reflect a unique difference in amyloidosis pathology, dependent on organ involvement. In SSA, amyloid fibers present a high percentage of ATTR fragments starting at position 46, 49 and 52, with the presence of a widely variable proportion of full length TTR. There is still some controversy in knowing if the proteolytic cleavage occurs before or after the fibers formation, but according to our results is seems likely that it occurs already in the bloodstream, before fiber formation. We believe that the overexpression of extracellular chaperone is a hallmark of conformational diseases and that in the future the most effective therapies for these diseases will be based on preventive approaches rather than downstream solutions. Moreover these common features hold great potential to be used as biomarkers for amyloid diseases. ~~ Spontaneous intracerebral hemorrhage is associated with high morbidity and mortality. About 65% to 80% of spontaneous ICH locates at deep parenchyma structure, including the basal ganglia, thalamus, brainstem, and cerebellum. The causes of SDICH are most likely heterogeneous, including environmental and genetic factors. Recently, matrix metalloproteinases pathway has been shown to play multiple roles in remodeling of extracellular matrix, damage of blood-brain barrier, and inflammation reactions in spontaneous ICH. MMPs are a family of zinc/calcium dependent endopeptidases which function in the degradation of ECM given the ability of splintering matrix integrity. Among MMPs, gelatin-binding MMPs were particularly unique in BBB PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19776696 damage because of their ability to digest type IV and type V collagen. These collagen contents are the essential constituents of vascular basement membrane that is connected with surrounding smooth muscle cells in the vascular endothelium. MMP-9 participates not only in collagen integrity but also in interaction involving inflammation, reactive oxygen species, and nitric oxide. Several cell types in brain have the capacity to produce MMP-9, including endothelial cells, astrocytes, and microglial cells. Degradation of these collagen tissues is believed to be the beginning step for the breakdown of the vessel integrity, which PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19778700 is responsible for the 
eventual rupture of the vessel walls. Degradation of the vascular ECM by MMP-9 has also been suggested to be a cause for angiogenesis and vascular remodeling and may contribute to the development of unstable aneurismal vasculature and increase the risk of ICH. Immunohistochemistry showed higher levels of total MMP-9, active MMP-9, pro-MMP-9, and tissue inhibitors of metalloproteinases -1 and TIMP-3 in the brain arteriovenous malformations specimen than in the control samples. MMP-9 was also discovered in the endothelial and peri-endothelial cell layer and infiltrating neutrophils of brain AVM. The proteolytic effects of MMPs were modulated mainly by TIMPs. Each of the four reported endogenous TIMPs was able to interact with any of the MMPs; however, certain combinations between MMPs and TIMPs have been reported, in which TIMP-1 is the main endogenous inhibitor of MMP-9. Increased mRNA expression of both MMP-9 and TIMP-1 in cerebral aneurysms was found in animal models. In Chinese populations, whereas no association between MMP-9 gene and ICH susceptibility was
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