Cellular models of alpha‐synuclein toxicity and aggregation. Issue 5 (30th July 2019)

• Record Type: Journal Article
• Authors: Delenclos, Marion; Burgess, Jeremy D.; Lamprokostopoulou, Agaristi; Outeiro, Tiago F.; Vekrellis, Kostas; McLean, Pamela J.
• Other Names: Outeiro Tiago F. guestEditor.; Mestre Tiago A. guestEditor.
• Is Part Of: Journal of neurochemistry. Volume 150:Issue 5(2019)
• Page Start: 566
• Page End: 576
• Publication Date: 2019-07-30
• Subjects: cellular model -- dopaminergic neurons -- oligomers -- Parkinson's disease -- α‐Synuclein; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.14806
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Misfolding and aggregation of alpha‐synuclein (α‐synuclein) 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 role in pathogenesis and disease progression, the function of α‐synuclein and the molecular mechanisms underlying α‐synuclein‐induced neurotoxicity in these diseases are still elusive. Many in vitro and in vivo experimental models mimicking α‐synuclein pathology such as oligomerization, toxicity and more recently neuronal propagation have been generated over the years. In particular, cellular models have been crucial for our comprehension of the pathogenic process of the disease and are beneficial for screening of molecules capable of modulating α‐synuclein toxicity. Here, we review α‐synuclein based cell culture models that reproduce some features of the neuronal populations affected in patients, from basic unicellular organisms to mammalian cell lines and primary neurons, to the cutting edge models of patient‐specific cell lines. These reprogrammed cells known as induced pluripotent stem cells (iPSCs) have garnered attention because they closely reproduce the characteristics of neurons found in patients and provide a valuable tool for mechanistic studies. We also discuss how different cell models may constitute powerful tools for high‐throughput screening of molecules capable of modulating α‐synuclein toxicity and prevention of its propagation. This article is part of the Special Issue "Synuclein". Abstract : The ability to model cellular characteristics of synucleinopathies in a petri dish can offer myriad opportunities for studying pathogenic mechanisms and aid the development and validation of future pharmacological interventions. Here, we review available cellular models to study α‐synuclein toxicity from basic unicellular organisms to mammalian cell linesand primary neurons, to more recent cellular systems such as human induced pluripotent stem cells. We describe the strategies employed to monitor and measure α‐synuclein–induced dysfunction and discuss how these models constitute powerful tools for high‐throughput screening of molecules capable of modulating α‐synuclein toxicity and preventing propagation. This article is part of the Special Issue "Synuclein".