Hypoxia and Inflammation as a Consequence of β-Fibril Accumulation: A Perspective View for New Potential Therapeutic Targets

Figure 1

Production and localization of β-fibrils. The drawing shows the intracellular and the extracellular localization of β-fibrils of amyloidosic substance as observed at the electron microscope in different β-fibrilloses. Transmission electron micrographs of β-fibril localization in the cytosol (tau tangles of Alzheimer’s disease) (a), in the cisternae of the endoplasmic reticulum (light chain polymers in a transformed B-lymphocyte/plasma cell) (b), and in the extracellular space (c) in close contact with a macrophage in the process of phagocytizing the fibrillar amyloid substance. Occasionally, β-fibrils have been observed in the mitochondrial matrix, being frequently organized as paracrystals (d, e). The nature of fibrillar protein is usually unknown. Mitochondria bearing fibril accumulation usually increase their volume, suggesting that accumulated misfolded fibrillar protein can be either imported from the cytosol or endogenously synthesized by mitochondrial machinery.