An inorganic overview of natural Aβ fragments: Copper(II) and zinc(II)-mediated pathways

Ubiquitin binds the amyloid β peptide and interferes with its clearance pathways

“…The enzymatic degradation of the amyloid peptide produced nine peptide fragments within 60 min of reaction (Table S3 in the ESI †). As previously described, 48 in the early stage of the IDEmediated hydrolysis, the main targeted regions encompass the hydrophobic Phe residues, the vicinal His residues, and, to a lesser extent, Asn27 and Met35 (Fig. 5A).…”

CuII Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function

“…Neurons and other brain cells take up Aβ peptides as a necessary step in BBB clearance, and intracellular digestion of these peptides via the ubiquitin–proteasome system (UPS) and the lysosomes has been demonstrated, as reviewed. , However, digestion of extracellular Aβ peptides by individual extracellular or external membrane-bound proteases has gained more attention as a possible culprit in AD and a facile target for intervention. In some cases, a relationship between the enzyme expression level and its activity or inhibition was correlated with the progression of disease in humans or experimental animals. ,− Proteases listed in the context of Aβ degradation include insulin-degrading enzyme (IDE), neprilysin (NEP), matrix metalloproteinases (MMPs), especially MMP2, MMP7, and MMP9, angiotensin-converting enzyme (ACE), endothelin-converting enzymes (ECE1 and ECE2), and plasmin. Indeed, the catabolic activity of any individual protease is not likely to suffice to account for AD pathology, but rather the actions of anabolic and catabolic enzymes sum up to a dynamic Aβ equilibrium level, which may evolve with age as malfunctions of various metabolic pathways, including proteolysis and clearance, accrue …”

“…Neurons and other brain cells take up Aβ peptides as a necessary step in BBB clearance, and intracellular digestion of these peptides via the ubiquitin−proteasome system (UPS) and the lysosomes has been demonstrated, as reviewed. 61,79 However, digestion of extracellular Aβ peptides by individual extracellular or external membrane-bound proteases has gained more attention as a possible culprit in AD and a facile target for intervention. In some cases, a relationship between the enzyme expression level and its activity or inhibition was correlated with the progression of disease in humans or experimental animals.…”

The Aggregation Pattern of Aβ1–40 is Altered by the Presence of N‐Truncated Aβ4–40 and/or CuII in a Similar Way through Ionic Interactions

“…[29,30] The term Ab does not represent as ingle peptide, but a broad family of peptides characterized by C-and N-terminal truncations/extensions and post-translationalm odifications. [31][32][33][34][35][36][37][38][39] The sequences of peptidess tudied in this work are presented in Ta ble 1, and they are compared with those of other representative peptideso ft he Ab family in Table S1 in the SupportingI nformation.…”