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

1 Citation (Scopus)

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

Fingerprint

Synucleins
alpha-Synuclein
Toxicity
Agglomeration
Neurons
Screening
Cells
Multiple System Atrophy
Lewy Bodies
Lewy Body Disease
Cell Line
Induced Pluripotent Stem Cells
Oligomerization
Molecules
Pathology
Cytotoxicity
Stem cells
Cell culture
Parkinson Disease
Disease Progression

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

Cellular models of alpha-synuclein toxicity and aggregation. / Delenclos, Marion; Burgess, Jeremy D.; Lamprokostopoulou, Agaristi; Outeiro, Tiago F.; Vekrellis, Kostas; McLean, Pamela J.

In: Journal of neurochemistry, Vol. 150, No. 5, 01.01.2019, p. 566-576.

Research output: Contribution to journalReview article

Delenclos, M, Burgess, JD, Lamprokostopoulou, A, Outeiro, TF, Vekrellis, K & McLean, PJ 2019, 'Cellular models of alpha-synuclein toxicity and aggregation', Journal of neurochemistry, vol. 150, no. 5, pp. 566-576. https://doi.org/10.1111/jnc.14806
Delenclos M, Burgess JD, Lamprokostopoulou A, Outeiro TF, Vekrellis K, McLean PJ. Cellular models of alpha-synuclein toxicity and aggregation. Journal of neurochemistry. 2019 Jan 1;150(5):566-576. https://doi.org/10.1111/jnc.14806
Delenclos, Marion ; Burgess, Jeremy D. ; Lamprokostopoulou, Agaristi ; Outeiro, Tiago F. ; Vekrellis, Kostas ; McLean, Pamela J. / Cellular models of alpha-synuclein toxicity and aggregation. In: Journal of neurochemistry. 2019 ; Vol. 150, No. 5. pp. 566-576.
@article{3b434c5d15a640d28f262cd4c09444fc,
title = "Cellular models of alpha-synuclein toxicity and aggregation",
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”.",
keywords = "cellular model, dopaminergic neurons, oligomers, Parkinson’s disease, α-Synuclein",
author = "Marion Delenclos and Burgess, {Jeremy D.} and Agaristi Lamprokostopoulou and Outeiro, {Tiago F.} and Kostas Vekrellis and McLean, {Pamela J}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/jnc.14806",
language = "English (US)",
volume = "150",
pages = "566--576",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Cellular models of alpha-synuclein toxicity and aggregation

AU - Delenclos, Marion

AU - Burgess, Jeremy D.

AU - Lamprokostopoulou, Agaristi

AU - Outeiro, Tiago F.

AU - Vekrellis, Kostas

AU - McLean, Pamela J

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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”.

AB - 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”.

KW - cellular model

KW - dopaminergic neurons

KW - oligomers

KW - Parkinson’s disease

KW - α-Synuclein

UR - http://www.scopus.com/inward/record.url?scp=85070911631&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070911631&partnerID=8YFLogxK

U2 - 10.1111/jnc.14806

DO - 10.1111/jnc.14806

M3 - Review article

C2 - 31265132

AN - SCOPUS:85070911631

VL - 150

SP - 566

EP - 576

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -