Olive Component Oleuropein Promotes β-Cell Insulin Secretion and Protects β-Cells from Amylin Amyloid-Induced Cytotoxicity

Wu, Ling; Velander, Paul; Liu, Dongmin; Xu, Bin

doi:10.1021/acs.biochem.7b00199

Cited by 53 publications

(46 citation statements)

References 21 publications

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“…PD results mostly from the aggregation of α-synuclein into intracellular Lewy bodies found in the neurons of the mesencephalic substantia nigra. Actually, olive polyphenols, notably OLE and its main metabolite, HT, have been reported to be effective against amyloid aggregation and the ensuing pathologic effects in T2DM [11,12], AD [13][14][15][16][17][18][19] and, possibly, in PD [20,21] and other amyloidoses. Plant polyphenols, including those enriched in EVOO, have also been reported to reduce insulin resistance and to improve impaired glucose homeostasis, two main signs of T2DM.…”

Section: Polyphenols: Important Players Of the Mediterranean/asian Dietsmentioning

confidence: 99%

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Leri

Scuto

Ontario

et al. 2020

IJMS

326

213

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The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer’s and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

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Section: Polyphenols: Important Players Of the Mediterranean/asian Dietsmentioning

confidence: 99%

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Leri

Scuto

Ontario

et al. 2020

IJMS

326

213

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“…Recently, several studies have suggested that natural phenolic compounds can interfere with the amyloid aggregation process both by affecting the amyloid intermediate formation and promoting the aggregation cascade towards nontoxic species [58,59]. In particular, the main phenolic compounds of extra-virgin olive oil, i.e., oleuropein aglycone (OleA) and its main metabolite, hydroxytyrosol (3,4-dihydroxyphenylethanol (HT), aside from their biological and pharmacological properties, have been shown to affect the amyloid aggregation process in different model proteins in vitro [12,[15][16][17][18][19][20][21]60]. Because only little information is available for HT compared to OleA, in this study, we tested the molecular effect of HT in the amyloid aggregation process of human insulin.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, HT has been shown to affect the amyloid aggregation process in hen egg white lysozyme, Aβ 1-42 , Amylin, Tau protein and α-synuclein [15][16][17][18]20,21]. In particular, HT has been suggested to interact with these amyloidogenic proteins and affect amyloid intermediate formation as well as promote the formation of off-pathway species unable to induce cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…HT ( Figure 1) is also highly concentrated in red wine and can be endogenously produced via dopamine metabolism [10,11]. Recently, OleA and HT have been shown to affect the amyloid aggregation process in different model proteins in vitro although the molecular mechanisms have been poorly characterized [12][13][14][15][16][17][18][19][20][21]. Because only little information is available for HT compared to OleA and considering that HT is one of the main metabolites of OleA, further studies could be useful for a better understanding of the antiamyloidogenic properties of this compound.…”

Section: Introductionmentioning

confidence: 99%

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Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Sirangelo

Borriello

Vilasi

2020

IJMS

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Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.

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“…Transmission Electron Microscopy (TEM) Analysis. TEM images were collected as previously described (Velander et al, 2016;Wu et al, 2017). Briefly, 30 µM human tau isoforms were incubated in 20 mM Tris-HCl, pH 7.4 for 10-12 days at 37 °C.…”

Section: Thioflavin-t Fluorescence Aggregationmentioning

confidence: 99%

Human Tau Isoform Aggregation and Selective Detection of Misfolded Tau from Post-Mortem Alzheimer’s Disease Brains

Wang

Lad

et al. 2020

Preprint

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Tau aggregates are present in a large number of neurodegenerative diseases known as "tauopathies", including Alzheimer's disease (AD). As there are six human tau isoforms in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions, we tested whether tau isoforms behave differently in aggregation. We discovered that all six tau isoforms are capable of forming PHF-tau like filaments and the 3R tau isoforms aggregate significantly faster than their 4R counterparts. We further mapped key segments of tau isoforms that contribute to their aggregation kinetics, where it was determined that microtubule binding domains R2 and R3 were the major contributors to tau aggregation. To evaluate the feasibility of using the six recombinant tau isoforms as substrates to amplify misfolded tau, we demonstrated that full-length human tau isoforms can seed and detect misfolded tau from the post-mortem AD brain tissues with high specificity by an ultrasensitive technology termed real-time quaking-induced conversion (RT-QuIC). Mass spectrometric analysis of PHF-tau samples extracted from AD brains identified peptides corresponding to all major forms of human brain tau isoforms along with a consensus hyperphosphorylated peptide near the C-terminus.Together, our findings not only reveal new aggregation kinetic properties of human tau isoforms, support the development of methods to quantitatively measure misfolded human tau isoforms in AD brains, but also uncover the capability of full-length human tau isoforms as substrates for "prion-like" tau seeding by RT-QuIC assays that may be used for new biomarker development for AD and other tauopathy diagnosis.

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Olive Component Oleuropein Promotes β-Cell Insulin Secretion and Protects β-Cells from Amylin Amyloid-Induced Cytotoxicity

Cited by 53 publications

References 21 publications

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin

Human Tau Isoform Aggregation and Selective Detection of Misfolded Tau from Post-Mortem Alzheimer’s Disease Brains

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