Environmental lead exposure aggravates the progression of Alzheimer's disease in mice by targeting on blood brain barrier

Wu, Shuqi; Liu, Huaixiang; Zhao, Heping; Wang, Xiaohui; Chen, Jingli; Xia, Dong; Chen, Xiao; Cheng, Jianding; Zhao, Zhiqiang; He, Yun

doi:10.1016/j.toxlet.2019.11.009

Cited by 37 publications

(18 citation statements)

References 32 publications

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“…[ [23][24][25][172][173][174] Manganese Manganese exposure increased the transcription of BACE1 in PC12 cells [27] Silver nanoparticles Silver nanoparticle exposure increased the protein expression of BACE1 [32] Zinc Zinc exposure increased BACE1 in mice and SH-SY5Y cells [175] Pesticides, fungicides, herbicides DDT DDT exposure increased BACE1 levels in SH-SY5Y cells [33] Paraquat Paraquat treatment altered BACE1 subcellular compartmentalization [36] Rotenone Rotenone treatment facilitated BACE1 expression and activity [34] Residues of cyprodinil, mepanipyrim, and pyrimethanil…”

Section: Metalsmentioning

confidence: 99%

Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target

Syeda

Cannon

2021

J Biochem & Molecular Tox

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Alzheimer's disease (AD) is a major public health crisis due to devastating cognitive symptoms, a lack of curative treatments, and increasing prevalence. Most cases are sporadic (>95% of cases) after the age of 65 years, implicating an important role of environmental factors in disease pathogenesis. Environmental neurotoxicants have been implicated in neurodegenerative disorders including Parkinson's Disease and AD. Animal models of AD and in vitro studies have shed light on potential neuropathological mechanisms, yet the biochemical and molecular underpinnings of AD‐relevant environmental neurotoxicity remain poorly understood. Beta‐site amyloid precursor protein cleaving enzyme 1 (BACE1) is a potentially critical pathogenic target of environmentally induced neurotoxicity. BACE1 clearly has a critical role in AD pathophysiology: It is required for amyloid beta production and expression and activity of BACE1 are increased in the AD brain. Though the literature on BACE1 in response to environmental insults is limited, current studies, along with extensive AD neurobiology literature suggest that BACE1 deserves attention as an important neurotoxic target. Here, we critically review research on environmental neurotoxicants such as metals, pesticides, herbicides, fungicides, polyfluoroalkyl substances, heterocyclic aromatic amines, advanced glycation end products, and acrolein that modulate BACE1 and potential mechanisms of action. Though more research is needed to clearly understand whether BACE1 is a critical mediator of AD‐relevant neurotoxicity, available reports provide convincing evidence that BACE1 is altered by environmental risk factors associated with AD pathology, implying that BACE1 inhibition and its use as a biomarker should be considered in AD management and research.

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Section: Metalsmentioning

confidence: 99%

Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target

Syeda

Cannon

2021

J Biochem & Molecular Tox

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“…Ujiie, et al reported that BBB permeability precedes senile plaque formation in an AD mice model [24]. Wu, et al recently showed the role of BBB in lead induced AD-like pathology [25]. A recent study by shin and colleagues also reported BBB dysfunction in a 3D human neural cell culture micro luidic in vitro model of AD [26].…”

Section: Chronic Neurodegenerative Diseasesmentioning

confidence: 98%

Central nervous system diseases associated with blood brain barrier breakdown - A Comprehensive update of existing literatures

Dutta¹

2020

J Neurosci Neurol Disord

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Blood vessels that supply and feed the central nervous system (CNS) possess unique and exclusive properties, named as blood–brain barrier (BBB). It is responsible for tight regulation of the movement of ions, molecules, and cells between the blood and the brain thereby maintaining controlled chemical composition of the neuronal milieu required for appropriate functioning. It also protects the neural tissue from toxic plasma components, blood cells and pathogens from entering the brain. In this review the importance of BBB and its disruption causing brain pathology and progression to different neurological diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) etc. will be discussed.

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“…Numerous metal exposures can result in the occurrence of AD, ranging from aluminum, zinc, mercury to lead [8,25,26]. A growing body of evidence supported close relations of AD patients and higher lead exposure.…”

Section: Ad and Lead Exposurementioning

confidence: 99%

“…Lead can cause a variety of adverse outcome on central nervous system (CNS), and is regarded as an important environmental insult leading to multiple neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), attention deficit/hyperactivity disorder (ADHD), etc. [7][8][9][10][11][12]. Lead is a risk factor of CNS-related diseases even with a very low exposure level, and the current "safe" level is 5 mg/dl for children, as proposed by Centers for Disease Control and Prevention (CDC) [13].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Basis of Lead-Induced Neurological Disorders

Wang

Zhang

2020

IJERPH

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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.

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Environmental lead exposure aggravates the progression of Alzheimer's disease in mice by targeting on blood brain barrier

Cited by 37 publications

References 32 publications

Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target

Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target

Central nervous system diseases associated with blood brain barrier breakdown - A Comprehensive update of existing literatures

Epigenetic Basis of Lead-Induced Neurological Disorders

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