Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid

Mital, Mariusz; Bal, Wojciech; Frączyk, Tomasz; Drew, Simon C.

doi:10.1021/acs.inorgchem.8b00391

Cited by 30 publications

(43 citation statements)

References 43 publications

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“…This has been shown by high-performance liquid chromatography analysis yielding several product peaks after incubation of Aβ 1-40 with either recombinant soluble NEP produced in Sf9 cells or NEP purified from rabbit kidney cortex (46). More recent studies using synthetic Aβ peptides and recombinant human NEP confirmed the generation of Aβ peptide fragments starting with Phe-4 (such as Aβ 4-9 or Aβ 4-16 but also the existence of several other cleavage sites, at least under the given in vitro conditions (48,49). Therefore, it is currently unclear whether NEP might contribute to the generation of longer Aβ peptides such as Aβ 4-40 and Aβ 4-42 .…”

Section: Aβ 4-xmentioning

confidence: 96%

N-Terminally Truncated Aß Peptide Variants in Alzheimer’s Disease

Wirths

Zampar

Weggen

2019

Alzheimer’s Disease

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The accumulation and aggregation of amyloid-β (Aβ) peptides in the brain is believed to be the initial trigger in the molecular pathology of Alzheimer' s disease (AD). In addition to the widely studied full-length Aβ peptides (mainly Aβ 1-40 and Aβ 1-42), a variety of amino-terminally truncated (N-truncated) peptides, such as Aβ pE3-x and Aβ 4-x , have been detected in high abundance in autopsy samples from sporadic and familial AD patients. N-truncated Aβ species adopt specific physicochemical properties resulting in a higher aggregation propensity and increased peptide stability, which likely account for their neurotoxic potential. The presence of N-truncated Aβ peptides in transgenic mouse models of AD and the selective overexpression of specific N-truncated variants in the murine brain have facilitated their investigation in relevant in vivo settings. In this chapter, we address the pathological relevance of N-truncated Aβ peptide species and summarize the current knowledge about the enzymatic activities that might be involved in their generation.

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Section: Aβ 4-xmentioning

confidence: 96%

N-Terminally Truncated Aß Peptide Variants in Alzheimer’s Disease

Wirths

Zampar

Weggen

2019

Alzheimer’s Disease

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“…An imbalance in the levels of copper and zinc has been linked to Alzheimer’s disease (AD) (Mital et al, 2018; Sensi et al, 2018) [54,55]. Pathogenesis of Alzheimer’s disease involves accumulation of the β-amyloid (Aβ) peptide in the brain.…”

Section: Copper Levels In Alcoholismmentioning

confidence: 99%

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review

et al. 2019

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The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.

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“…We are aware of several such XHH sequences in human proteins/peptides, of which two were demonstrated to form very high affinity 4N complexes ( c K7.4 > 10 14 M -1 ): endostatin (SHH-) and amyloid-β12-x (VHH-), one of the prominent products of enzymatic amyloid-β degradation. [25][26][27] Coordination properties of these hybrid ATCUN with biologically relevant N ligands (His for instance) warrant further investigations.…”

Section: Figurementioning

confidence: 99%