Chemistry and Physics of Lipids, Год журнала: 2021, Номер 237, С. 105083 - 105083
Опубликована: Апрель 19, 2021
Язык: Английский
Chemical Reviews, Год журнала: 2021, Номер 121(13), С. 8285 - 8307
Опубликована: Июнь 17, 2021
This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures elucidated from various in vitro ex vivo obtained fibrils. In parallel, fibril formation has studied under highly artificial but comparatively reproducible conditions. The starts with a summary what is known speculated aggregation experiments. A partially hypothetic selection model be described that may suitable to explain why amyloid look way they do, particular, at least all so far reported high cryo-electron microscopy register, cross-β-sheet mostly consist two protofilaments twisted around each other. An intrinsic feature prion-like nature assemblies. Transferring point view situation not straightforward, hypothetic, leaves many open questions need addressed future.
Язык: Английский
Процитировано
158
Biomolecules, Год журнала: 2024, Номер 14(3), С. 320 - 320
Опубликована: Март 8, 2024
Antimicrobial peptides (AMPs), as well host defense (HDPs), constitute the first line of part innate immune system. Humans are known to express antimicrobial precursor proteins, which further processed generate AMPs, including several types α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity is crucial defend against infections caused by pathogenic bacteria, viruses, fungi, parasites. emergence multi-drug resistant bacteria global concern for public health. prospects targeting antibiotic-resistant strains with high significance developing new generations agents. 37-residue long LL37, only cathelicidin family AMP in humans, has been major focus past few decades research. LL37 likely underscored its expression throughout body, spanning from epithelial cells various organs—testis, skin, respiratory tract, gastrointestinal tract—to cells. Remarkably, apart canonical direct killing organisms, exerts other activities, inflammatory response modulation, chemo-attraction, wound healing closure at infected sites. In addition, derived bestowed anti-cancer anti-amyloidogenic properties. this review article, we aim develop integrative, mechanistic insight into peptides, based on biophysical, structural, functional studies recent years. We believe that will pave way future research structures, biochemical biophysical properties, design novel LL37-based molecules.
Язык: Английский
Процитировано
28
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Фев. 24, 2022
Human islet amyloid polypeptide (hIAPP) self-assembles into fibrils which deposit in pancreatic islets of type 2 diabetes (T2D) patients. Here, we applied chemical kinetics to study the mechanism assembly wild-type hIAPP and its more amyloidogenic natural variant S20G. We show that aggregation both peptides involves primary nucleation, secondary nucleation elongation. also report discovery two structurally distinct small-molecule modulators assembly, one delaying wt hIAPP, but not S20G; while other enhances rate variants at substoichiometric concentrations. Investigation inhibition mechanism(s) using kinetics, native mass spectrometry, fluorescence titration, SPR NMR revealed inhibitor retards elongation, by binding peptide monomers. By contrast, accelerator predominantly interacts with species formed lag phase. These compounds represent useful tools may serve as promising starting-points for development therapeutics T2D.
Язык: Английский
Процитировано
48
Journal of Cellular and Molecular Medicine, Год журнала: 2023, Номер 27(13), С. 1775 - 1789
Опубликована: Май 21, 2023
Abstract Parkinson's disease (PD) is the second most common neurodegenerative after Alzheimer's (AD). Genetic predisposition and immune dysfunction are involved in pathogenesis of PD. Notably, peripheral inflammatory disorders neuroinflammation associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) due to hyperglycaemia‐induced oxidative stress release pro‐inflammatory cytokines. Particularly, insulin resistance (IR) T2DM promotes degeneration dopaminergic neurons substantia nigra (SN). Thus, T2DM‐induced predispose development progression PD, their targeting may reduce risk T2DM. Therefore, this narrative review aims find potential link between by investigating role signalling pathways, mainly nuclear factor kappa B (NF‐κB) nod‐like receptor pyrin 3 (NLRP3) inflammasome. NF‐κB implicated T2DM, activation induction neuronal apoptosis was also confirmed patients. Systemic NLRP3 inflammasome accumulation α‐synuclein SN. Increasing patients enhances interleukin (IL)‐1β followed systemic inflammation neuroinflammation. In conclusion, NF‐κB/NLRP3 axis could be causal pathway The mechanisms triggered activated lead pancreatic β‐cell attenuation changes inhibiting early future risk.
Язык: Английский
Процитировано
40
Diabetology & Metabolic Syndrome, Год журнала: 2023, Номер 15(1)
Опубликована: Май 13, 2023
Abstract Human Islet amyloid polypeptide (hIAPP) from pancreatic β cells in the islet of Langerhans has different physiological functions including inhibiting release insulin and glucagon. Type 2 diabetes mellitus (T2DM) is an endocrine disorder due to relative insufficiency resistance (IR) associated with increased circulating hIAPP. Remarkably, hIAPP structural similarity beta (Aβ) can engage pathogenesis T2DM Alzheimer’s disease (AD). Therefore, present review aimed elucidate how acts as a link between AD. IR, aging low cell mass increase expression which binds membrane leading aberrant Ca 2+ activation proteolytic enzymes series events causing loss cells. Peripheral plays major role AD, high level AD risk patients. However, there no hard evidence for brain-derived Nevertheless, oxidative stress, mitochondrial dysfunction, chaperon-mediated autophagy, heparan sulfate proteoglycan (HSPG), immune response, zinc homeostasis could be possible mechanisms induction aggregation risk. In conclusion, increasing levels patients predispose them development progression Dipeptidyl peptidase 4 (DPP4) inhibitors glucagon-like peptide-1 (GLP-1) agonists attenuate by deposition hIAP.
Язык: Английский
Процитировано
39
Journal of Molecular Biology, Год журнала: 2024, Номер 436(14), С. 168475 - 168475
Опубликована: Фев. 3, 2024
Язык: Английский
Процитировано
11
Advances in Colloid and Interface Science, Год журнала: 2024, Номер 331, С. 103205 - 103205
Опубликована: Май 23, 2024
Язык: Английский
Процитировано
10
Biophysical Chemistry, Год журнала: 2021, Номер 281, С. 106735 - 106735
Опубликована: Ноя. 30, 2021
Язык: Английский
Процитировано
45
Critical Reviews in Food Science and Nutrition, Год журнала: 2022, Номер 63(26), С. 7878 - 7895
Опубликована: Март 25, 2022
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated interrelationships responsible for initiating its pathogenesis. Novel strategies the treatment of this devastating have attracted increasing attention worldwide. Anthocyanins are bioactive compounds that widely distributed in plant kingdom, and multiple studies elucidated their beneficial role preventing managing T2DM. This review summarizes comments on hypoglycemic actions anthocyanins from perspective molecular mechanisms different target-related signaling pathways vitro, vivo, clinical trials. can ameliorate T2DM by functioning as carbohydrate digestive enzyme inhibitors, facilitating glucose transporter 4 (GLUT4) translocation, suppressing effectiveness dipeptidyl peptidase IV (DPP-IV), promoting glucagon-like peptide-1 (GLP-1) secretion, inhibiting protein tyrosine phosphatase 1B (PTP1B) overexpression, interacting sodium-glucose co-transporter (SGLT) to delay absorption various organs tissues. In summary, anthocyanin promising practical small molecule hyperglycemic symptoms accompanying complications suffered patients diabetes. However, rational potent doses daily intake required future.
Язык: Английский
Процитировано
33
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2022, Номер 1868(11), С. 166485 - 166485
Опубликована: Июль 13, 2022
Amyloid oligomers and fibrils are protein aggregates that cause an onset progression of many neurodegenerative diseases, diabetes type 2 systemic amyloidosis. Although a growing body evidence shows trigger mitochondrial dysfunction simultaneously enhancing production reactive oxygen species, exact mechanisms by which these exert their toxicities remain unclear. In this study, we used advanced microscopic spectroscopic methods to examine topography structure insulin grown in the lipid-free environment, as well presence major classes phospho- sphingolipids. We also employed set molecular markers determine extent induce damage cell endoplasmic reticulum (ER), important organelle for calcium storage, synthesis folding. Our results show activate expression Activating Transcription Factor 6 (ATF6), transmembrane is involved unfolded response (UPR) stressed ER. At same time, two other ER proteins, Inositol Requiring 1 (IRE1α) eLF2a, product PKR-like kinase (PERK), exhibited very low levels. Furthermore, amyloid 78-kDa glucose-regulated GRP78, UPR. observed UPR-induced proapoptotic transcription factor CHOP, which, turn, regulates caspase 3 BCL2 family members, including localized Bax. These findings UPR-associated stress ultimately fatal changes homeostasis.
Язык: Английский
Процитировано
32