From Small Peptides to Large Proteins against Alzheimer’sDisease

Picone, Pasquale; Sanfilippo, Tiziana; Vasto, Sonya; Baldassano, Sara; Guggino, Rossella; Nuzzo, Domenico; Bulone, Donatella; Biagio, Pier Luigi San; Muscolino, Emanuela; Monastero, Roberto; Dispenza, Clelia; Giacomazza, Daniela

doi:10.3390/biom12101344

Cited by 7 publications

(2 citation statements)

References 221 publications

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“…Among them, Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and tau aggregates in the brain of patients . Although the exact cause of AD remains unknown, inhibiting tau aggregation is a potential therapeutic strategy. − So far, various molecules have been tested for their potency to inhibit tau aggregation, including natural products. − …”

Section: Introductionmentioning

confidence: 99%

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

Chen

et al. 2023

J. Agric. Food Chem.

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The microtubule-associated protein tau is involved in Alzheimer’s disease and other tauopathies. Recently, tau has been shown to undergo liquid–liquid phase separation (LLPS), which is implicated in the physiological function and pathological aggregation of tau. In this report, we demonstrate that the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) promotes the formation of liquid tau droplets at neutral pH by creating a network of hydrophobic interactions and hydrogen bonds, mainly with the proline-rich domain of tau. We further show that EGCG oxidation, tau phosphorylation, and the chemical structure of the polyphenol influence the efficacy of EGCG in facilitating tau LLPS. Complementary to the inhibitory activity of EGCG in tau fibrillization, our findings provide novel insights into the biological activity of EGCG and offer new clues for future studies on the molecular mechanism by which EGCG alleviates neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

Chen

et al. 2023

J. Agric. Food Chem.

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“…Significant examples are found in the literature, illustrating important and innovative chemical-biological studies. They include small peptides and large protein effects in Alzheimer's disease (Picone et al, 2022), emergence of bimolecular condensates as attractive targets for drug discovery (Mitrea…”

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confidence: 99%

Editorial: Specialty grand challenge: Structure, spectroscopy, and imaging

Ferreira

2023

Front. Chem. Biol.

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In the interdisciplinary field of chemical biology, different scientists, generally chemists and biologists, undertake their best efforts to develop advanced methodologies and innovative approaches to address important scientific goals and societal demands. Furthermore, confronting the complexity of problems to be solved and sophisticated systems to be discerned, the partnership of diverse other specialists is demanded, including physicists, spectroscopists, pharmacologists, and physicians. Collectively, their complemented work brings together several areas of research, experimental as well as theoretical, to accomplish higher levels of knowledge about the structural and functional characterization of biological systems. A profound understanding of life and its wide-ranging processes are their final aims.Recently, AlphaFold, a revolutionary artificial intelligence (AI) network, predicted the structures of more than 200 million proteins in a universe of 1 million species, reaching to determine the protein structures of nearly every organism with known protein sequence data. It made it possible to understand the relationships between protein functions and its 3D structures, and the results are now available to scientists in a database (Callaway, 2022). These data can certainly encourage numerous types of studies in the future.A significant example of the structural feature's importance in basic and applied investigations is the development of messenger RNA (mRNA)-based therapeutics (Dammes and Peer, 2020). Since its discovery in the 1960s, improvements in its engineering to express therapeutic proteins or manipulate specific genes' expression have enabled a broad range of applications in intractable diseases, such as severe infections, varied forms of cancer, and genetic diseases, besides new vaccines, and accelerate its clinical translation (Kim, 2022;Qin, Tang, Chen et al., 2022). Because of the unfavorable characteristics of mRNA's, such as large size, instability, immunogenicity, sensitivity to enzymatic degradation by RNases, and limited cellular uptake, many pivotal issues had to be solved during the development of mRNA-based therapeutics. Additionally, a variety of delivery strategies, including nanolipids, exosomes, or polymeric micelles as carriers, was crucial for their wide applicability (Uchida et al., 2020).Moreover, investigations in this chemico-biological field frequently lead to the conception, design, and provision of new molecules capable of interacting efficiently with selected biomolecules, and consequently causing remarkable modifications in their functional behavior. Results can establish new parameters and lead to new drugs that are more efficient, safe, and selective in facing illnesses and syndromes. Significant examples are found in the literature, illustrating important and innovative chemical-biological studies. They include small peptides and large protein effects in Alzheimer's disease (Picone et al., 2022), emergence of bimolecular condensates as attractive targets for drug discovery...

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Investigation of the expression of Cis P‐tau and Pin1 proteins following air pollution induction in the brain tissue of C57BL/6 mice

Shahpasand,

Khatami,

Ehtiati

et al. 2024

Biotech and App Biochem

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Alzheimer's disease (AD) is a multifactorial disease in which environmental factors play a role. Among environmental factors, air pollution is a vital issue in modern life. Despite extensive considerations, it remains uncertain how pollution mediates neurodegeneration in AD. Beta‐amyloids and hyperphosphorylated tau proteins are the two main pathological markers that have been studied in AD so far. Tau protein is basically a phosphoprotein whose functions are controlled by phosphorylation. The function of tau protein is to be located on the surface of microtubules and stabilize them. Studies have shown that phosphorylated tau protein (p‐tau) exists in cis and trans conformations at Thr231, among which cis is highly neurotoxic. The Pin1 enzyme performs the conversion of cis to trans or vice versa. In this study, an experimental mouse model was designed to investigate the formation of cis p‐tau by inducing air pollution. In this way, mice were randomly exposed to pollution at 2‐week, 1‐month, and 2‐month intervals. We investigated the formation of phosphorylated cis tau form during air pollution on mouse brains using Western blots and immunofluorescence. The fluorescent imaging results and Western blotting analysis of mouse brains revealed a significant accumulation of cis p‐tau in pollution‐treated mice models compared to the healthy control mice. According to Western blot results, air pollution induction caused a significant decrease in Pin1 protein. The results clearly show that the tauopathy observed during air pollution is mediated through the formation of cis tau. Our findings unravel tauopathy mysteries upon pollution and would help find a possible therapeutic target to fight the devastating disorder caused by modern life.

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From Small Peptides to Large Proteins against Alzheimer’sDisease

Cited by 7 publications

References 221 publications

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

(−)-Epigallocatechin-3-gallate, a Polyphenol from Green Tea, Regulates the Liquid–Liquid Phase Separation of Alzheimer’s-Related Protein Tau

Editorial: Specialty grand challenge: Structure, spectroscopy, and imaging

Investigation of the expression of Cis P‐tau and Pin1 proteins following air pollution induction in the brain tissue of C57BL/6 mice

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