Toxicology Letters 230 (2014) 85–103 Contents lists available at ScienceDirect Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet Pesticides exposure as etiological factors of Parkinson’s disease and other neurodegenerative diseases—A mechanistic approach Maria Teresa Baltazar a,b,∗ , Ricardo Jorge Dinis-Oliveira a,b,c,d , Maria de Lourdes Bastos a , Aristidis M. Tsatsakis e , José Alberto Duarte f , Félix Carvalho a,∗∗ a REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal b IINFACTS – Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences-North (ISCS-N), CESPU, CRL, Gandra, Portugal c Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal d Forensic Sciences Center – CENCIFOR, Portugal e Toxicology Department, Medical School, University of Crete, Heraklion, Crete, Greece f CIAFEL, Faculty of Sports, University of Porto, Porto, Portugal highlights • The review provides new information regarding the neurotoxicity mecha- nisms of herbicides and pesticides. • New perspectives concerning chronic pesticide exposure with amyotrophic lateral sclerosis. • Novel information regarding paraquat exposure and Parkinson’s disease. • New insights regarding chronic pes- ticide exposure and Alzheimer’s dis- ease. graphical abstract article info Article history: Available online 3 February 2014 Keywords: Pesticides Paraquat Parkinson’s disease Alzheimer’s disease Amyotrophic lateral sclerosis Neurodegenerative diseases abstract The etiology of most neurodegenerative disorders is multifactorial and consists of an interaction between environmental factors and genetic predisposition. The role of pesticide exposure in neurodegenerative disease has long been suspected, but the specific causative agents and the mechanisms underlying are not fully understood. For the main neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis there are evidences linking their etiology with long-term/low- dose exposure to pesticides such as paraquat, maneb, dieldrin, pyrethroids and organophosphates. Most of these pesticides share common features, namely the ability to induce oxidative stress, mitochondrial dysfunction, -synuclein fibrillization and neuronal cell loss. This review aims to clarify the role of pes- ticides as environmental risk factors in genesis of idiopathic PD and other neurological syndromes. For this purpose, the most relevant epidemiological and experimental data is highlighted in order to discuss the molecular mechanisms involved in neurodegeneration. © 2014 Elsevier Ireland Ltd. All rights reserved. ∗ Corresponding author at: REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. ∗∗ Corresponding author. E-mail addresses: mteresabaltazar@gmail.com, baltazarmtp@gmail.com (M.T. Baltazar), felixdc@ff.up.pt (F. Carvalho). 1. Introduction The World Health Organization currently estimates that around a billion people worldwide are affected by a neurodegenerative disease (WHO, 2006). As aging corresponds to the greatest risk factor for neurodegeneration, the prevalence of neurological disor- ders is expected to increase dramatically in next few years due to 0378-4274/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxlet.2014.01.039