Physiological cholesterol concentration is a neuroprotective factor against β-amyloid and β-amyloid–metal complexes toxicity

Granzotto, Alberto; Suwalsky, Mario; Zatta, Paolo

doi:10.1016/j.jinorgbio.2011.05.013

Cited by 14 publications

(11 citation statements)

References 50 publications

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“…Zn(II) or Cu(II) ion binding has been shown to structurally convert the C-terminal part of Aβ into a helical conformation inside the membrane, thus preventing formation of the β-sheet structures considered important for aggregation [70]. Binding to other metal ions has also been shown to affect the structure of Aβ species in membranes and their related cytotoxicity [71]. Metal ion bridges between oligomeric species might bring together and stabilize pore structures in the membrane environment [70,72].…”

Section: Membrane Pore Formation and Metal Ionsmentioning

confidence: 99%

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

et al. 2019

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The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.

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Section: Membrane Pore Formation and Metal Ionsmentioning

confidence: 99%

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

et al. 2019

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“…Further to this, APP intracellular domain AICD was found to regulate cholesterol levels via LRP1 (Grosgen et al, 2010). However, there also are data reporting that cholesterol in physiological concentrations can protect neuronal cells against Aβ-induced toxicity and slow down the process of formation of toxic aggregates of Aβ with metal ions, in particular with aluminum (Granzotto et al, 2011). This correlates with the data suggesting that cholesterol may have a protective effect against membrane disruption by amyloid species (in this case, Aβ-derived diffusible ligands: ADDLs).…”

Section: Lipid Raft Components and Their Changes In Admentioning

confidence: 99%

Lipid Rafts and Alzheimer’s Disease: Protein-Lipid Interactions and Perturbation of Signaling

Hicks¹,

Nalivaeva²,

Turner³

2012

Front. Physio.

171

176

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Lipid rafts are membrane domains, more ordered than the bulk membrane and enriched in cholesterol and sphingolipids. They represent a platform for protein-lipid and protein–protein interactions and for cellular signaling events. In addition to their normal functions, including membrane trafficking, ligand binding (including viruses), axonal development and maintenance of synaptic integrity, rafts have also been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD). Lipid rafts promote interaction of the amyloid precursor protein (APP) with the secretase (BACE-1) responsible for generation of the amyloid β peptide, Aβ. Rafts also regulate cholinergic signaling as well as acetylcholinesterase and Aβ interaction. In addition, such major lipid raft components as cholesterol and GM1 ganglioside have been directly implicated in pathogenesis of the disease. Perturbation of lipid raft integrity can also affect various signaling pathways leading to cellular death and AD. In this review, we discuss modulation of APP cleavage by lipid rafts and their components, while also looking at more recent findings on the role of lipid rafts in signaling events.

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“…URE2p, found in S. Cerevisiae , plays a role in nitrogen catabolism. Pmel17, found in humans, plays a role in melanin synthesis [ 3 , 4 , 5 ]. On the other hand, clinical and molecular studies have revealed a diverse group of detrimental amyloids, which cause protein misfolding in amyloid-driven diseases.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas

et al. 2022

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Amyloidosis is a common pathological event in which proteins self-assemble into misfolded soluble and insoluble molecular forms, oligomers and fibrils that are often toxic to cells. Notably, aggregation-prone human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic hormone linked to islet β-cells demise in diabetics. The unifying mechanism by which amyloid proteins, including hIAPP, aggregate and kill cells is still matter of debate. The pathology of type-2 diabetes mellitus (T2DM) is characterized by extracellular and intracellular accumulation of toxic hIAPP species, soluble oligomers and insoluble fibrils in pancreatic human islets, eventually leading to loss of β-cell mass. This review focuses on molecular, biochemical and cell-biology studies exploring molecular mechanisms of hIAPP synthesis, trafficking and degradation in the pancreas. In addition to hIAPP turnover, the dynamics and the mechanisms of IAPP–membrane interactions; hIAPP aggregation and toxicity in vitro and in situ; and the regulatory role of diabetic factors, such as lipids and cholesterol, in these processes are also discussed.

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Physiological cholesterol concentration is a neuroprotective factor against β-amyloid and β-amyloid–metal complexes toxicity

Cited by 14 publications

References 50 publications

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

Lipid Rafts and Alzheimer’s Disease: Protein-Lipid Interactions and Perturbation of Signaling

Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas

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