Membrane pores in the pathogenesis of neurodegenerative disease.

摘要: The neurodegenerative diseases described in this volume, as well many nonneurodegenerative diseases, are characterized by deposits known amyloid. Amyloid has long been associated with these various a pathological marker and implicated directly the molecular pathogenesis of disease. However, increasing evidence suggests that proteinaceous Congo red staining may not be toxic or destructive tissue. Recent studies strongly implicate smaller aggregates amyloid proteins species underlying diseases. Despite outward obvious differences among clinical syndromes, there some striking similarities their pathologies. These include dysregulation intracellular calcium levels, impairment mitochondrial function, ability virtually all peptides to form ion-permeable pores lipid membranes. Pore formation is enhanced environmental factors promote protein aggregation inhibited agents, such red, which prevent aggregation. Remarkably, formed variety from other share common set physiologic properties. irreversible insertion membranes, heterodisperse pore sizes, inhibition formation, blockade zinc, relative lack ion selectivity voltage dependence. Although exists information about physical structure pores, modeling 4-6-mer subunits assemble into 24-mer pore-forming aggregates. resemble β-barrel toxics bacterial toxins, staphylococcal α-hemolysin, anthrax toxin, Clostridium perfringolysin.