Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Radiolaria and Phaeodaria

Polycystina (~400–800 living species and several thousand extinct forms) and Phaeodaria (~400–500 living species) are exclusively marine, open-ocean planktonic protists, most of which possess elaborate siliceous skeletons. The cytoplasm is divided into an internal part (endoplasm) separated from the external, more vacuolated one (ectoplasm) by a perforated membrane – the central capsule. The Polycystina protrude long and slender cytoplasmic projections (axopodia) supported internally by a rigid central rod (axoneme); while the Phaeodria have anetwork ofperipheral finely interconnectedpseudopodia.Afew Polycystina are colonial, but most, as well as all Phaeodaria, are solitary, around 40 μm to almost 2 mm in size. Most polycystine species peak in abundance between 0 and 100 m, whereasphaeodarianstendtolivedeeper,oftenbelow300m.Polycystineshavea rich fossil record dating from the Cambrian and are important for stratigraphic, paleoecologic, and evolutionary studies. The world-wide biogeography and diversity of radiolarians is chiefly governed by water temperature. Radiolarian prey includes bacteria, algae, protozoa, and microinvertebrates. Many surfacedwelling species of Polycystina possess symbiotic algae and photosynthetic cyanobacteria that provide nourishment to the host. Some colonial radiolaria reproduce by binary fission of the central capsules. Sexual reproduction of polycystines or Phaeodaria has not been confirmed, but the release of motile swarmers, likely gametes, has been widely documented. In species with a radial symmetry (Spumellaria) shell-growth is centrifugal, whereas in the Nassellaria the internal cephalic elements and the cephalis appear first. Individual longevity is estimated to range between 2 and 3 weeks and 1–2 months