Cellular models of alpha-synuclein toxicity and aggregation

Marion Delenclos, Jeremy D. Burgess, Agaristi Lamprokostopoulou, Tiago F. Outeiro, Kostas Vekrellis, Pamela J McLean

Research output: Contribution to journalReview article

4 Scopus citations

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. (Figure presented.). This article is part of the Special Issue “Synuclein”.

Original languageEnglish (US)
Pages (from-to)566-576
Number of pages11
JournalJournal of neurochemistry
Volume150
Issue number5
DOIs
StatePublished - Jan 1 2019

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Keywords

  • cellular model
  • dopaminergic neurons
  • oligomers
  • Parkinson’s disease
  • α-Synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Delenclos, M., Burgess, J. D., Lamprokostopoulou, A., Outeiro, T. F., Vekrellis, K., & McLean, P. J. (2019). Cellular models of alpha-synuclein toxicity and aggregation. Journal of neurochemistry, 150(5), 566-576. https://doi.org/10.1111/jnc.14806