Epigenetic Basis of Lead-Induced Neurological Disorders
Open Access
- 6 July 2020
- journal article
- review article
- Published by MDPI AG in International Journal of Environmental Research and Public Health
- Vol. 17 (13), 4878
- https://doi.org/10.3390/ijerph17134878
Abstract
Environmental lead (Pb) exposure is closely associated with pathogenesis of a range of neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), attention deficit/hyperactivity disorder (ADHD), etc. Epigenetic machinery modulates neural development and activities, while faulty epigenetic regulation contributes to the diverse forms of CNS (central nervous system) abnormalities and diseases. As a potent epigenetic modifier, lead is thought to cause neurological disorders through modulating epigenetic mechanisms. Specifically, increasing evidence linked aberrant DNA methylations, histone modifications as well as ncRNAs (non-coding RNAs) with AD cases, among which circRNA (circular RNA) stands out as a new and promising field for association studies. In 23-year-old primates with developmental lead treatment, Zawia group discovered a variety of epigenetic changes relating to AD pathogenesis. This is a direct evidence implicating epigenetic basis in lead-induced AD animals with an entire lifespan. Additionally, some epigenetic molecules associated with AD etiology were also known to respond to chronic lead exposure in comparable disease models, indicating potentially interlaced mechanisms with respect to the studied neurotoxic and pathological events. Of note, epigenetic molecules acted via globally or selectively influencing the expression of disease-related genes. Compared to AD, the association of lead exposure with other neurological disorders were primarily supported by epidemiological survey, with fewer reports connecting epigenetic regulators with lead-induced pathogenesis. Some pharmaceuticals, such as HDAC (histone deacetylase) inhibitors and DNA methylation inhibitors, were developed to deal with CNS disease by targeting epigenetic components. Still, understandings are insufficient regarding the cause–consequence relations of epigenetic factors and neurological illness. Therefore, clear evidence should be provided in future investigations to address detailed roles of novel epigenetic factors in lead-induced neurological disorders, and efforts of developing specific epigenetic therapeutics should be appraised.Funding Information
- Fundamental Research Funds for the Central Universities (JZ2020HGTB0053)
- National Key Basic Research Program of China (No. 2018YFC1602204)
This publication has 168 references indexed in Scilit:
- Alteration of the microRNA network during the progression of Alzheimer's diseaseEMBO Molecular Medicine, 2013
- Genome-wide expression and methylation profiling in the aged rodent brain due to early-life Pb exposure and its relevance to agingMechanisms of Ageing and Development, 2012
- An epigenetic blockade of cognitive functions in the neurodegenerating brainNature, 2012
- Prenatal environmental exposures, epigenetics, and diseaseReproductive Toxicology, 2011
- Regulation of chromatin by histone modificationsCell Research, 2011
- Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosineNature Biotechnology, 2011
- Epigenetic changes in Alzheimer's disease: Decrements in DNA methylationNeurobiology of Aging, 2010
- Molecular Neurobiology of Lead (Pb2+): Effects on Synaptic FunctionMolecular Neurobiology, 2010
- Ginkgo biloba for Attention-Deficit/Hyperactivity Disorder in children and adolescents: A double blind, randomized controlled trialProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2010
- HDAC2 negatively regulates memory formation and synaptic plasticityNature, 2009