Neurotoxicity Research

, Volume 27, Issue 3, pp 328–354 | Cite as

Neurotoxin Mechanisms and Processes Relevant to Parkinson’s Disease: An Update

  • Juan Segura-AguilarEmail author
  • Richard M. Kostrzewa


The molecular mechanism responsible for degenerative process in the nigrostriatal dopaminergic system in Parkinson’s disease (PD) remains unknown. One major advance in this field has been the discovery of several genes associated to familial PD, including alpha synuclein, parkin, LRRK2, etc., thereby providing important insight toward basic research approaches. There is an consensus in neurodegenerative research that mitochon dria dysfunction, protein degradation dysfunction, aggregation of alpha synuclein to neurotoxic oligomers, oxidative and endoplasmic reticulum stress, and neuroinflammation are involved in degeneration of the neuromelanin-containing dopaminergic neurons that are lost in the disease. An update of the mechanisms relating to neurotoxins that are used to produce preclinical models of Parkinson´s disease is presented. 6-Hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and rotenone have been the most wisely used neurotoxins to delve into mechanisms involved in the loss of dopaminergic neurons containing neuromelanin. Neurotoxins generated from dopamine oxidation during neuromelanin formation are likewise reviewed, as this pathway replicates neurotoxin-induced cellular oxidative stress, inactivation of key proteins related to mitochondria and protein degradation dysfunction, and formation of neurotoxic aggregates of alpha synuclein. This survey of neurotoxin modeling—highlighting newer technologies and implicating a variety of processes and pathways related to mechanisms attending PD—is focused on research studies from 2012 to 2014.


Parkinson’s disease 6-Hydroxydopamine MPP+ MPTP Ortho-quinones Reactive oxygen species Rotenone 



Mitochondrial membrane potential






5-Hydroxytryptamine, serotonin




Apoptosis-inducing factor


Adenosine monophosphate


AMP activated protein kinase


Apoptosis signal-regulating kinase 1


Activating transcription factor


Brain-derived neurotrophic factor


Calcium ion


C/EBP homologous protein






Dopamine transporter




l-3,4-Dihydroxyphenylacetic acid

EP1 receptor

Prostaglandin E subtype 1 receptor


Endoplasmic reticulum


Extracellular signal-regulated kinase


Glial-derived neurotrophic factor


Glial fibrillary acidic protein


Glucose regulatory protein 78


Heme oxygenase-1


Heat shock protein


Human uncoupling protein


Homovanillic acid




Mitogen-activated protein kinase


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion




Mammalian target of rapamycin


Reduced nicotinamide adenine dinucleotide phosphate


Neuronal nitric oxide synthase


Poly-ADP-ribose polymerase


Parkinson’s disease


Phosphorylated ERK


Prostaglandin E


PTEN-induced kinase


cAMP-dependent protein kinase A


Peroxisome proliferator-activated receptor


Regulated endocrine-specific protein


Reactive oxygen species


Sphingosine-1 phosphate


p70 S6 kinase 1


Pars compacta Substantia nigra


Tyrosine hydroxylase


Tyrosine hydroxylase immunoreactivity




Tumor necrosis factor- α


TNF receptor-associated protein


Ubiquitin carboxy-terminal hydrolase L-1


Vascular endothelial growth factor receptor-2


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Molecular and Clinical Pharmacology, ICBM, Faculty of MedicineUniversity of ChileSantiago 7Chile
  2. 2.Department of Biomedical Sciences, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA

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