Mapping of Photochemically-Derived Dityrosine across Fe-Bound N-Acetylated α-Synuclein

Curry, Alyson M.; Fernández, Ricardo D.; Pagani, Talita D; Abeyawardhane, Dinendra L; Trahan, Morgan L; Lucas, Heather R.

doi:10.3390/life10080124

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…The other cytokines, hormones or growth factors, and micro ribonucleic acids are also involved in the pathophysiology of PCOS, such as vascular epithelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), interleukin (IL), adipocytokine family (chemerin, omentin-1, leptin, adiponectin, and others), leptin, differentially expressed in normal and neoplastic development (DENND), RAS-related protein 5b (RAB5B), and small noncoding micro ribonucleic acid (microRNAs, miRNAs, and miR), including miR-130b-3p [68,71,73]. Since gene expression is controlled and modified by epigenetic factors, the post-translational modifications of proteins, such as methylation [74], acetylation [75], glycosylation [76], and sialylation [77], involved in turning the switch "on" or "off", are also reported to play a role in the pathophysiology of PCOS [71,73].…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Seow¹,

Chang

Chen

et al. 2020

IJMS

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Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5–10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5–15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30–90% and final pregnancy rates of 13–88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of “toxic” follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the “hypothalamus–pituitary–ovary” axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.

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Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Seow¹,

Chang

Chen

et al. 2020

IJMS

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“…Additionally, PICUP allows the analysis of the oligomers in their native state, without any attached cross-linker that could alter the oligomeric structures or affect the amyloid fibril formation process. PICUP has therefore been used for comparing oligomer distribution of native and mutant species, ,,,,− ,,, evaluating the effect of inhibitors or other factors on oligomer formation, ,,,− ,,,,− ,,,,, generating covalent oligomers of defined size, ,,,,, developing methods to detect covalent dimers in patients, understanding metal binding to α-synuclein, , and comparing different Aβ sources. , …”

Section: Introductionmentioning

confidence: 99%

“…PICUP was first demonstrated in 1999 in the study of the hexameric recombination protein uvsY, followed by many studies using the technique to study the oligomeric pattern of various other proteins. − Since then, PICUP has been used for diverse purposes, including the mapping of protein–ligand interactions, − the labeling and topographic study of G-coupled receptors, the preparation of covalently bound dimeric monoclonal antibodies, and for the polymerization of poly( l -tyrosine) silica particles . Furthermore, this method has been found to be especially useful for studying oligomerization of amyloidogenic proteins, such as insulin, , prions, − human transthyretin, Tau, α-synuclein, − and amyloid β (Aβ). ,,− …”

Section: Introductionmentioning

confidence: 99%

Photo-Induced Cross-Linking of Unmodified α-Synuclein Oligomers

Ortigosa-Pascual,

Leiding,

Linse

et al. 2023

ACS Chem. Neurosci.

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Photo-induced cross-linking of unmodified proteins (PICUP) has been used in the past to study size distributions of protein assemblies. PICUP may, for example, overcome the significant experimental challenges related to the transient nature, heterogeneity, and low concentration of amyloid protein oligomers relative to monomeric and fibrillar species. In the current study, a reaction chamber was designed, produced, and used for PICUP reaction optimization in terms of reaction conditions and lighting time from ms to s. These efforts make the method more reproducible and accessible and enable the use of shorter reaction times compared to previous studies. We applied the optimized method to an α-synuclein aggregation time course to monitor the relative concentration and size distribution of oligomers over time. The data are compared to the time evolution of the fibril mass concentration, as monitored by thioflavin T fluorescence. At all time points, the smaller the oligomer, the higher its concentration observed after PICUP. Moreover, the total oligomer concentration is highest at short aggregation times, and the decline over time follows the disappearance of monomers. We can therefore conclude that these oligomers form from monomers.

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“…The excessive production of free radicals and reactive oxygen species (ROS) have been associated to the mechanisms leading to neuronal death, review by Abramov et al [ 10 ] Intracellular formation of ROS is also originated by metal imbalance. In the context of metal interactions by IDPs associated with neurodegenerative disease, Lucas and co-workers [ 11 ] investigated the process of dityrosine crosslinking of αS upon iron binding, with tyrosine 39 resulting as the main contributor to dityrosine and Y125 appearing to be involved in dityrosine crosslinks in unmetalated αS. Similarly important is the interaction of the Abeta IDP with copper(II).…”

mentioning

confidence: 99%