α-SYNUCLEIN 2.0 – Moving towards Cell-Type Specific Pathophysiology.

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• Glial α-synuclein promotes neurodegeneration characterized by a distinct transcriptional program in vivo. July 4, 2019 Related ArticlesGlial α-synuclein promotes neurodegeneration characterized by a distinct transcriptional program in vivo. Glia. 2019 Jul 03;: Authors: Olsen AL, Feany MB Abstract α-Synucleinopathies are neurodegenerative diseases that are characterized pathologically by α-synuclein inclusions in neurons and glia. The pathologic contribution of glial α-synuclein in these diseases is not well understood. Glial α-synuclein may be of particular importance in multiple…
• Glucocerebrosidase activity, cathepsin D and monomeric α-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation. October 22, 2019 Glucocerebrosidase activity, cathepsin D and monomeric α-synuclein interactions in a stem cell derived neuronal model of a PD associated GBA1 mutation. Neurobiol Dis. 2019 Oct 18;:104620 Authors: Yang SY, Gegg M, Chau D, Schapira A Abstract The presence of GBA1 gene mutations increases risk for Parkinson's disease (PD), but the pathogenic mechanisms of GBA1 associated PD remain unknown. Given that…
• A Vaccine for Parkinson's - Developments in Immunotherapy November 13, 2018 Alpha-synuclein is a protein which is abundant in the brain and throughout the body. It carries important functions, in relation to communication between neurons for example. When misfolded however, it becomes toxic to neurons and is a key pathological culprit in Parkinson’s. It is therefore an important target for disease modification. Immunotherapy in Parkinson's attempts to use immune cells, and…
• A Vaccine for Parkinson's - Developments in Immunotherapy November 13, 2018 Alpha-synuclein is a protein which is abundant in the brain and throughout the body. It carries important functions, in relation to communication between neurons for example. When misfolded however, it becomes toxic to neurons and is a key pathological culprit in Parkinson’s. It is therefore an important target for disease modification. Immunotherapy in Parkinson's attempts to use immune cells, and…
• Alpha-synuclein and Parkinson's August 17, 2017 What is Alpha-synuclein? Alpha-synuclein is a protein which is abundant in the human brain. It is also present in other body tissues notably the heart, muscle and gut. In the brain it tends to be concentrated near the tips of the nerve cells (neurons) in association with synaptic vesicles which are responsible for the release of chemicals between neurons -…
• Alpha-synuclein and Parkinson's August 17, 2017 What is Alpha-synuclein? Alpha-synuclein is a protein which is abundant in the human brain. It is also present in other body tissues notably the heart, muscle and gut. In the brain it tends to be concentrated near the tips of the nerve cells (neurons) in association with synaptic vesicles which are responsible for the release of chemicals between neurons -…
• Cellular models of alpha-synuclein toxicity and aggregation. July 3, 2019 Cellular models of alpha-synuclein toxicity and aggregation. J Neurochem. 2019 Jul 02;: Authors: Delenclos M, Burgess JD, Lamprokostopoulou A, Outeiro TF, Vekrellis K, McLean PJ Abstract Misfolding and aggregation of alpha-synuclein (α-syn) with concomitant cytotoxicity is a hallmark of Lewy body related disorders such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Although it plays a pivotal…
• Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated α-Synuclein. June 19, 2019 Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated α-Synuclein. PLoS Biol. 2019 Jun 18;17(6):e3000318 Authors: Birol M, Wojcik SP, Miranker AD, Rhoades E Abstract Cell-to-cell transmission of toxic forms of α-Synuclein (αS) is thought to underlie disease progression in Parkinson disease. αS in humans is constitutively N-terminally acetylated (αSacetyl), although the impact of this modification is…
• How is alpha-synuclein cleared from the cell? May 10, 2019 Related ArticlesHow is alpha-synuclein cleared from the cell? J Neurochem. 2019 May 08;: Authors: Stefanis L, Emmanouilidou E, Pantazopoulou M, Kirik D, Vekrellis K, Tofaris GK Abstract The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different…
• Alpha-synuclein oligomers: a new hope October 16, 2017 A report part funded by The Cure Parkinson's Trust assesses the evidence for the toxicity and prion-like activity of oligomeric forms of alpha-synuclein and discusses the advances in our understanding of the role of alpha-synuclein in Parkinson’s and current approaches being taken to therapeutically target alpha-synuclein oligomers and their implications. Read the full report here: ncbi.nlm.nih.gov/pubmed/28803412
• Alpha-synuclein oligomers: a new hope October 16, 2017 A report part funded by The Cure Parkinson's Trust assesses the evidence for the toxicity and prion-like activity of oligomeric forms of alpha-synuclein and discusses the advances in our understanding of the role of alpha-synuclein in Parkinson’s and current approaches being taken to therapeutically target alpha-synuclein oligomers and their implications. Read the full report here: ncbi.nlm.nih.gov/pubmed/28803412
• [Prion Properties of Alpha-Synuclein]. June 12, 2019 [Prion Properties of Alpha-Synuclein]. Mol Biol (Mosk). 2019 May-Jun;53(3):380-387 Authors: Schwarzman AL, Senkevich KA, Emelyanov AK, Pchelina SN Abstract The prion properties of alpha-synuclein, a key aggregating protein involved in the pathogenesis of so-called synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, and its various conformers are discussed. It is shown that alpha-synuclein may be transferred…
• α-Synuclein Pathology in Parkinson's Disease and Related α-Synucleinopathies. June 7, 2019 Related Articlesα-Synuclein Pathology in Parkinson's Disease and Related α-Synucleinopathies. Neurosci Lett. 2019 Jun 03;:134316 Authors: Henderson MX, Trojanowski JQ, Lee VM Abstract Over 20 years ago, the synaptic protein α-synuclein was identified as the primary component of the Lewy bodies (LBs) that are a sine qua non of Parkinson's disease (PD). Since that time, extensive research has demonstrated that α-synuclein…
• Autophagy activation promotes clearance of α-synuclein inclusions in fibril-seeded human neural cells. August 4, 2019 Related ArticlesAutophagy activation promotes clearance of α-synuclein inclusions in fibril-seeded human neural cells. J Biol Chem. 2019 Aug 02;: Authors: Gao J, Perera G, Bhadbhade M, Halliday GM, Dzamko N Abstract There is much interest in delineating the mechanisms by which the α-synuclein protein accumulates in brains of individuals with Parkinson's disease (PD). Preclinical studies with rodent and primate models…
• Interactions between iron and α-synuclein pathology in Parkinson's disease. June 25, 2019 Interactions between iron and α-synuclein pathology in Parkinson's disease. Free Radic Biol Med. 2019 Jun 22;: Authors: Chen B, Wen X, Jiang H, Wang J, Song N, Xie J Abstract Both iron deposition and α-synuclein aggregation are neuropathological hallmarks of Parkinson's disease (PD). We aimed to summarize the extensive interactions between these two factors. The direct structural links between iron…
• Genetic Manipulators of Alpha Synuclein November 25, 2019 In the brains of people with Parkinson's, there is an accumulation of alpha synuclein protein. It clusters and aggregates together forming dense circular objects inside neurons called Lewy bodies. This build up of alpha synuclein is believed to play a role in the neurodegeneration associated with Parkinson's. Researchers have previously conducted large screening studies to identify genes that could be…
• Effect of Osmolytes on Conformational Behavior of Intrinsically Disordered Protein α-Synuclein. November 9, 2019 Related ArticlesEffect of Osmolytes on Conformational Behavior of Intrinsically Disordered Protein α-Synuclein. Biophys J. 2019 Oct 22;: Authors: Jahan I, Nayeem SM Abstract α-Synuclein is an intrinsically disordered protein whose function in a healthy brain is poorly understood. It is genetically and neuropathologically linked to Parkinson's disease (PD). PD is manifested after the accumulation of plaques of α-synuclein aggregates in…
• E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease. June 27, 2019 E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease. PLoS One. 2019;14(6):e0218261 Authors: Sakai R, Suzuki M, Ueyama M, Takeuchi T, Minakawa EN, Hayakawa H, Baba K, Mochizuki H, Nagai Y Abstract Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which is characterized by progressive…
• Identification of a New α-Synuclein Aggregation Inhibitor via Mass Spectrometry-based Screening. May 24, 2019 Related ArticlesIdentification of a New α-Synuclein Aggregation Inhibitor via Mass Spectrometry-based Screening. ACS Chem Neurosci. 2019 May 22;: Authors: Xu M, Loa-Kum-Cheung W, Zhang H, Quinn RJ, Mellick GD Abstract The aggregation of disordered α-synuclein protein is pathogenically connected with Parkinson's disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of α-synuclein is an active research area in…
• Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone. July 18, 2019 Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone. Brain. 2019 Jul 15;: Authors: Lee JS, Kanai K, Suzuki M, Kim WS, Yoo HS, Fu Y, Kim DK, Jung BC, Choi M, Oh KW, Li Y, Nakatani M, Nakazato T, Sekimoto S, Funayama M, Yoshino H, Kubo SI, Nishioka K, Sakai R, Ueyama M, Mochizuki H, Lee…