229 1. ABSTRACT Mercury intoxication is a serious public health problem and a worldwide concern. The Minamata Convention on Mercury has been signed by 128 countries and endorsed by the World Health Organization with the recommendation of promoting the management of epidemiological information. The Central Nervous System is the main target organ for mercury. Symptoms of intoxication include altered motor coordination, visual and tactile dysfunction and paralysis, caused by neurodegeneration with a key role for oxidative damage. Recently, some studies have demonstrated a correlation between mercury intoxication and isoforms of apolipoprotein E (ApoE). In this review, epidemiological data and hypotheses about the possible molecular mechanisms underlying the association between ApoE and mercury intoxication are assessed. Based on the evidence and the neuropathological changes that the presence of ApoE4 and mercury neurotoxicity have in common, we propose a convergent action of both factors. ApoE4 seems to potentiate the damage caused by mercury. Increased knowledge of this interaction using epidemiological and pre-clinical studies is essential to improve prevention strategies to adequately manage intoxicated patients. 2. INTRODUCTION The etiology of many neurodegenerative disorders is still unclear and the role of the environment as a putative risk factor is being increasingly studied. Exposure to heavy metals, for example, is now recognized as a potential etiologic factor for some of them, such as Alzheimer’s disease (AD) (1, 2); Parkinson disease (3) and amyotrophic lateral sclerosis (4). Mercury, aluminum, cadmium and arsenic have been studied in AD due to their ability to increase amyloid-beta (Aβ) peptide and to produce abnormal forms of tau protein, causing senile/amyloid plaques and neurofbrillary tangles, respectively (1). Potential gene-environment interactions have been investigated extensively in the pathogenesis of some of these diseases. For example, apolipoprotein E4 (ApoE4) is the only genetic risk factor confrmed to play a role in the development of late onset Alzheimer’s disease, increasing the risk level by three-fold in heterozygous Role for apolipoprotein E in neurodegeneration and mercury intoxication Gabriela de Paula Fonseca Arrifano 1 , Marcus Augusto de Oliveira 2 , Jose Rogerio Souza-Monteiro 1 , Ricardo S. Oliveira Paraense 1 , Andrea Ribeiro-dos-Santos 3 , Jose Ricardo dos Santos Vieira 4 , Artur Luiz da Costa Silva 5 , Manoel da Silva Filho 6 , Barbarella de Matos Macchi 7 , Jose Luiz Martins do Nascimento 7 , Rommel Mario Rodriguez Burbano 8 , Maria Elena Crespo-Lopez 1 1 Laboratorio de Farmacologia Molecular, Instituto de Ciencias Biologicas (ICB), Universidade Federal do Para (UFPA), Belem, Brazil, 2 Laboratorio de Investigacoes em Neurodegeneracao e Infeccao, Universidade Federal do Para (UFPA), Belem, Brazil, 3 Laboratorio de Genética Humana e Medica, Universidade Federal do Para (UFPA), Belem, Brazil, 4 Laboratorio de Analises Clinicas, Universidade Federal do Para (UFPA), Belem, Brazil, 5 Laboratorio de Genomica e Bioinformatica, Universidade Federal do Para (UFPA), Belem, Brazil, 6 Laboratorio de Biofísica Celular, Universidade Federal do Para (UFPA), Belem, Brazil, 7 Laboratorio de Neuroquimica Molecular e Celular, Universidade Federal do Para (UFPA), Belem, Brazil, 8 Laboratorio de Citogenetica Humana, Instituto de Ciencias Biologicas (ICB), Universidade Federal do Para (UFPA), Belem, Brazil TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Mercury: A worldwide concern 4. Neurobiology of apolipoprotein E 5. Apolipoprotein E4 and mercury poisoning 6. New Perspectives: Our Hypothesis 7. Conclusion 8. Acknowledgements 9. References [Frontiers In Bioscience, Elite, 10, 229-241, January 1, 2018]