Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia.

The inflammatory response in prion diseases is dominated by microglial activation. As macrophages of the central nervous system, the phagocytic capacity of microglia is well recognized, and it is possible that microglia are involved in the removal and processing of amyloid fibrils, thus preventing their harmful effect. We have analyzed the effects of a synthetic peptide of the human prion protein, PrP(106-126), which can form fibrils, and the pathogenic form of prion protein, PrPsc, on phagocytosis in microglia isolated from neonatal rat brain cultures.

Chromogranin A-activated microglial cells induce neuronal apoptosis.

Chromogranin (CgA), a protein upregulated in many neuropathologies, can induce an activated phenotype in microglial cells that leads to neuronal apoptosis. The death-signaling pathways mobilized in neurons involve the death receptor Fas, p38 MAP kinase, and mitochondrial cytochrome c. We propose that CgA represents a potent endogenous inflammatory factor responsible for neuronal degeneration.