scholarly journals Molecular Mechanisms of Environmental Metal Neurotoxicity: A Focus on the Interactions of Metals with Synapse Structure and Function

Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 198
Author(s):  
Asuncion Carmona ◽  
Stéphane Roudeau ◽  
Richard Ortega

Environmental exposure to neurotoxic metals and metalloids such as arsenic, cadmium, lead, mercury, or manganese is a global health concern affecting millions of people worldwide. Depending on the period of exposure over a lifetime, environmental metals can alter neurodevelopment, neurobehavior, and cognition and cause neurodegeneration. There is increasing evidence linking environmental exposure to metal contaminants to the etiology of neurological diseases in early life (e.g., autism spectrum disorder) or late life (e.g., Alzheimer’s disease). The known main molecular mechanisms of metal-induced toxicity in cells are the generation of reactive oxygen species, the interaction with sulfhydryl chemical groups in proteins (e.g., cysteine), and the competition of toxic metals with binding sites of essential metals (e.g., Fe, Cu, Zn). In neurons, these molecular interactions can alter the functions of neurotransmitter receptors, the cytoskeleton and scaffolding synaptic proteins, thereby disrupting synaptic structure and function. Loss of synaptic connectivity may precede more drastic alterations such as neurodegeneration. In this article, we will review the molecular mechanisms of metal-induced synaptic neurotoxicity.

2018 ◽  
Vol 115 (16) ◽  
pp. E3827-E3836 ◽  
Author(s):  
Seok Heo ◽  
Graham H. Diering ◽  
Chan Hyun Na ◽  
Raja Sekhar Nirujogi ◽  
Julia L. Bachman ◽  
...  

Memory formation is believed to result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a subset of long-lived proteins (LLPs). While it is known that LLPs exist, whether such proteins are present at synapses is unknown. We performed an unbiased screen using metabolic pulse-chase labeling in vivo in mice and in vitro in cultured neurons combined with quantitative proteomics. We identified synaptic LLPs with half-lives of several months or longer. Proteins in synaptic fractions generally exhibited longer lifetimes than proteins in cytosolic fractions. Protein turnover was sensitive to pharmacological manipulations of activity in neuronal cultures or in mice exposed to an enriched environment. We show that synapses contain LLPs that may underlie stabile long-lasting changes in synaptic structure and function.


2008 ◽  
Vol 65 (6) ◽  
pp. 412-419 ◽  
Author(s):  
R Schutte ◽  
T Nawrot ◽  
T Richart ◽  
L Thijs ◽  
H A Roels ◽  
...  

2021 ◽  
Vol 134 (16) ◽  

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Fanny Jaudon and Martina Albini are co-first authors on ‘ A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor’, published in JCS. Fanny is a postdoc at the University of Trieste in the lab of Lorenzo A. Cingolani at Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genova, Italy, investigating the molecular mechanisms controlling development and function of neuronal circuits and implementing genome-editing approaches for the treatment of neurological disorders. Martina is a PhD student at the Istituto Italiano di Tecnologia in the lab of Fabio Benfenati and Fabrizia Cesca investigating neurotrophin biology and its involvement in neurological diseases.


2020 ◽  
Author(s):  
Inga Boll ◽  
Pia Jensen ◽  
Veit Schwämmle ◽  
Martin R. Larsen

AbstractSynaptic transmission leading to release of neurotransmitters in the nervous system is a fast and highly dynamic process. Previously, protein interaction and phosphorylation have been thought to be the main regulators of synaptic transmission. Here we show a novel potential modulator of synaptic transmission, sialylation of N-linked glycosylation. The negatively charged sialic acids can be modulated, similarly to phosphorylation, by the action of sialyltransferases and sialidases thereby changing local structure and function of membrane glycoproteins. We characterized site-specific alteration in sialylation on N-linked glycoproteins in isolated rat nerve terminals after brief depolarization using quantitative sialiomics. We identified 1965 formerly sialylated N-linked glycosites in synaptic proteins and found that the abundances of 430 glycosites changed after five seconds depolarization. We observed changes on essential synaptic proteins such as synaptic vesicle proteins, ion channels and transporters, neurotransmitter receptors and cell adhesion molecules. This study is to our knowledge the first to describe ultra-fast site-specific modulation of the sialiome after brief stimulation of a biological system.


2010 ◽  
Vol 43 (4) ◽  
pp. 341-352 ◽  
Author(s):  
Charu Misra ◽  
Sophie Restituito ◽  
Jainne Ferreira ◽  
Gerald A. Rameau ◽  
Jie Fu ◽  
...  

2000 ◽  
Vol 13 (1) ◽  
pp. 16-34 ◽  
Author(s):  
Martin M. Dinges ◽  
Paul M. Orwin ◽  
Patrick M. Schlievert

SUMMARY This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.


2020 ◽  
Vol 126 (4) ◽  
pp. 533-551 ◽  
Author(s):  
Haobo Li ◽  
Margaret H. Hastings ◽  
James Rhee ◽  
Lena E. Trager ◽  
Jason D. Roh ◽  
...  

During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.


2018 ◽  
Vol 84 (7) ◽  
pp. 478-487 ◽  
Author(s):  
Kaichuan Zhu ◽  
Finn Peters ◽  
Severin Filser ◽  
Jochen Herms

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