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Agrochemicals, α-Synuclein, and Parkinson’s Disease

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Abstract

Epidemiological, population-based case–control, and experimental studies at the molecular, cellular, and organism levels revealed that exposure to various environmental agents, including a number of structurally different agrochemicals, may contribute to the pathogenesis of Parkinson’s disease (PD) and several other neurodegenerative disorders. The role of genetic predisposition in PD has also been increasingly acknowledged, driven by the identification of a number of disease-related genes [e.g., α-synuclein, parkin, DJ-1, ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1), and nuclear receptor-related factor 1]. Therefore, the etiology of this multifactorial disease is likely to involve both genetic and environmental factors. Various neurotoxicants, including agrochemicals, have been shown to elevate the levels of α-synuclein expression in neurons and to promote aggregation of this protein in vivo. Many agrochemicals physically interact with α-synuclein and accelerate the fibrillation and aggregation rates of this protein in vitro. This review analyzes some of the aspects linking α-synuclein to PD, provides brief structural and functional descriptions of this important protein, and represents some data connecting exposure to agrochemicals with α-synuclein aggregation and PD pathogenesis.

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Abbreviations

AFM:

Atomic force microscopy

AD:

Alzheimer’s disease

ATP:

Adenosinetriphosphate

ATR–FTIR:

Attenuated total reflectance Fourier transform infrared

BBB:

Blood–brain barrier

BHC:

Benzene hexachloride

CD:

Circular dichroism

CK:

Casein kinase

CNS:

Central nervous system

DDC:

Diethyldithiocarbamate

DDE:

Dichlorodiphenyldichloroethylene (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene)

DDT:

Dichloro diphenyl trichloroethane

DLB:

Dementia with Lewy bodies

EDCs:

Endocrine disrupting chemicals

ER:

Endoplasmic reticulum

ETC:

Electron transport chain

HCH:

Hexachloro-cyclohexane

MAO-B:

Monoamine oxidase B

Mn-EBDC:

Manganese ethylene-bis-dithiocarbamate

MPP+ :

1-Methyl-4-phenylpyridinium ion

MPTP:

1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine

NAC:

Non-amyloid component

6-OHDA:

6-Hydroxydopamine

PANN:

Pesticide Action Network of North America

PD:

Parkinson’s disease

PLD2 :

Phospholipase D2

PQ•+ :

Paraquat monocation free radical

ROS:

Reactive oxygen species

TEM:

Transmission electron microscopy

TMAO:

Trimethylamine oxide

UCH-L1:

Ubiquitin C-terminal hydrolase isozyme l1

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Acknowledgments

We are extremely grateful to Alexey V. Uversky for careful reading and editing this manuscript. This work was supported in part by the Program of the Russian Academy of Sciences for the “Molecular and Cellular Biology” (to V.N.U.).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, 95064, USA

    Blanca A. Silva & Anthony L. Fink

  2. Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 7, Tampa, FL, 33612-4799, USA

    Leonid Breydo & Vladimir N. Uversky

  3. Byrd Alzheimer’s Research Institute, College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Vladimir N. Uversky

  4. Institute for Biological Instrumentation, Russian Academy of Sciences, 142292, Pushchino, Moscow Region, Russia

    Vladimir N. Uversky

Authors
  1. Blanca A. Silva
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  2. Leonid Breydo
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  3. Anthony L. Fink
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  4. Vladimir N. Uversky
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Correspondence to Vladimir N. Uversky.

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Prof. Anthony L. Fink has passed away on March 2, 2008

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Silva, B.A., Breydo, L., Fink, A.L. et al. Agrochemicals, α-Synuclein, and Parkinson’s Disease. Mol Neurobiol 47, 598–612 (2013). https://doi.org/10.1007/s12035-012-8333-2

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  • DOI: https://doi.org/10.1007/s12035-012-8333-2

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