Review: structure of amyloid fibril in diseases

Abstract

Tissue deposition of normally soluble proteins, or their fragments, as insoluble amyloid fibrils causes both acquired and hereditary systemic amyloidoses, which is usually fatal. Amyloid is associated with serious diseases such as Alzheimer's disease, type 2 diabetes, Parkinson's Disease, Huntington's Disease, cancer and the transmissible spongiform encephalopathies. Information concerning the structure and mechanism of formation of fibrils in these diseases is critical for understanding the process of pathology of the amyloidoses and to the development of more effective therapeutic agents that target the underlying disease mechanisms. Structural models have been made using information from a wide variety of techniques, including electron microscopy, X-ray diffraction, solid state NMR, and Congo red and CD spectroscopy. Although each type of amyloidosis is characterised by a specific amyloid fibril protein, the deposits share pathognomonic histochemical properties and the structural morphology of all amyloid fibrils is very similar. In fact, the structural similarity that defines amyloid fibres exists principally at the level of β-sheet folding of the polypeptides within the protofilament, while the different types vary in the supramolecular assembly of their protofilaments.

Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases

“…This incredible level of conformational plasticity is also a hallmark of other amyloidogenic proteins, such as amyloid β (Aβ; encoded by APP ) involved in Alzheimer disease and the prion protein (PrP; encoded by PRNP ) involved in Creutzfeldt–Jakob disease and prion infections (Ref. 6). Some amyloidogenic proteins (Alzheimer Aβ peptides, α-synuclein) belong to the IDP family; in other cases (e.g.…”

Amyloids of multiple species: are they helpful in survival?

“…CAG repeats‐containing huntingtin (Htt) protein also shows typical amyloidic features as observed in postmortem brains of Huntington's disease (HD) patients as well as in mouse models of the disease (Scherzinger et al, ; Ghahghaei & Faridi, ). Exon 1 of the 350 kDa Htt protein contains the CAG repeats, which are primarily involved in fibril formation, with flanking N‐terminal α‐helical structures providing assistance (Hoop et al, ).…”

Common Mechanisms in Neurodegenerative Diseases

“…[38][39][40] This capacity further increases the complexity of the problem we are facing, because it adds a new type of structure to proteins already characterized by high conformational versatility. [38][39][40] This capacity further increases the complexity of the problem we are facing, because it adds a new type of structure to proteins already characterized by high conformational versatility.…”