The modification of α-synuclein by dicarbonyl compounds inhibits its fibril-forming process

Lee, Daekyun; Park, Chang Wook; Paik, Seung R.; Choi, Kwan Yong

doi:10.1016/j.bbapap.2008.11.016

Cited by 92 publications

(57 citation statements)

References 29 publications

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“…α-syn is a lysine-rich protein and contains 15 residues that are putative glycation targets and is thus prone to aggregation. Indeed, recent in vitro studies have even shown that AGEs induce the aggregation of α-syn in vitro (Lee et al, 2009;Padmaraju et al, 2011). The pathogenesis of the disease remains largely unclear; however, a few potential molecular contributors such as RAGE have been proposed (Teismann et al, 2012;Gao et al, 2014).…”

Section: Rage In Parkinson's Diseasementioning

confidence: 97%

Receptor for advanced glycation end-products in neurodegenerative diseases

Juranek¹,

Ray²,

Banach

et al. 2015

Reviews in the Neurosciences

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AbstractThis review, for the first time, aims to summarize the current knowledge in the emerging field of RAGE (receptor for advanced glycation end-products) studies in neurodegeneration and neurodegenerative diseases. RAGE, a member of the multiligand cell surface immunoglobulin family, has been implicated in numerous pathological conditions – from diabetes and cardiovascular diseases to tumors and neurodegenerative disorders, such as Alzheimer’s disease, familial amyloid polyneuropathy, diabetic neuropathy, Parkinson’s disease, and Huntington’s disease. Until now, the detailed mechanisms of the contribution of RAGE to neurodegeneration remain elusive; however, mounting evidence suggests that its detrimental actions are triggered by its ligand interactions and contribute to increased neuroinflammation, neuronal degeneration, and apoptosis. Deciphering the role of RAGE in neurodegenerative disorders will be a milestone in our basic understanding of the mechanisms involved in the pathogenesis of neurodegeneration, helping to delineate molecular links between complex RAGE signaling pathways and neuronal dysfunction and neurodegeneration.

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Section: Rage In Parkinson's Diseasementioning

confidence: 97%

Receptor for advanced glycation end-products in neurodegenerative diseases

Juranek¹,

Ray²,

Banach

et al. 2015

Reviews in the Neurosciences

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“…Advanced glycation end products (Munch et al 2000; Shaikh and Nicholson 2008), modification of α-synuclein with dicarbonyl compounds glyoxal and methylglyoxal (Lee et al 2009), and ribosylation of α-synuclein (Chen et al 2010) induce cross-linking of recombinant α-synuclein in vitro, accelerating aggregation, and causing cytotoxicity (Munch et al 2000; Shaikh and Nicholson 2008; Chen et al 2010; Padmaraju et al 2011). …”

Section: α-Synuclein Posttranslational Modificationsmentioning

confidence: 99%

Cell Biology and Pathophysiology of α-Synuclein

Burré

Sharma

Südhof

2017

Cold Spring Harb Perspect Med

420

384

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α-Synuclein is an abundant neuronal protein that is highly enriched in presynaptic nerve terminals. Genetics and neuropathology studies link α-synuclein to Parkinson’s disease (PD) and other neurodegenerative disorders. Accumulation of misfolded oligomers and larger aggregates of α-synuclein defines multiple neurodegenerative diseases called synucleino-pathies, but the mechanisms by which α-synuclein acts in neurodegeneration are unknown. Moreover, the normal cellular function of α-synuclein remains debated. In this perspective, we review the structural characteristics of α-synuclein, its developmental expression pattern, its cellular and subcellular localization, and its function in neurons. We also discuss recent progress on secretion of α-synuclein, which may contribute to its interneuronal spread in a prion-like fashion, and describe the neurotoxic effects of α-synuclein that are thought to be responsible for its role in neurodegeneration.

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“…Notably, α-syn is a lysine-rich protein and contains 15 residues that are putative glycation targets. Indeed, recent studies showed that AGEs induce the aggregation of α-syn in vitro [39,40]. Moreover, α-syn is rapidly glycated in the presence of D-ribose generating molten globule-like aggregations which cause cell oxidative stress and result in high cytotoxicity [41].…”

Section: Ages and Parkinson's Diseasementioning

confidence: 99%