Cobalt induces neurodegenerative damages through Pin1 inactivation in mice and human neuroglioma cells

Zheng, Fuli; Li, Yuqing; Zhang, Fengshun; Sun, Yi; Zheng, Chunyan; Luo, Zhousong; Wang, Yuan Liang; Aschner, Michael; Zheng, Hong; Lin, Liqiong; Cai, Ping; Shao, Wenya; Guo, Zhenkun; Zheng, Min; Zhou, Xiao Zhen; Lu, Kun Ping; Wu, Siying; Li, Huangyuan

doi:10.1016/j.jhazmat.2021.126378

Cited by 34 publications

(12 citation statements)

References 58 publications

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“…Cobalt is known to induce neurodegenerative damage in mice and human neuroglioma cells. 76 Studies on the analysis of trace elements present in the brain of AD patients have confirmed an elevated level of Cobalt. 77 Co 2+ -induced aggregation of human serum albumin has been reported.…”

Section: ■ Discussionmentioning

confidence: 98%

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities

Prajapati,

Mittal,

Ansari

et al. 2024

ACS Appl. Mater. Interfaces

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The essential amino acid histidine plays a central role in the manifestation of several metabolic processes, including protein synthesis, enzyme-catalysis, and key biomolecular interactions. However, excess accumulation of histidine causes histidinemia, which shows brain-related medical complications, and the molecular mechanism of such histidine-linked complications is largely unknown. Here, we show that histidine undergoes a self-assembly process, leading to the formation of amyloid-like cytotoxic and catalytically active nanofibers. The kinetics of histidine self-assembly was favored in the presence of Mg(II) and Co(II) ions. Molecular dynamics data showed that preferential noncovalent interactions dominated by H-bonds between histidine molecules facilitate the formation of histidine nanofibers. The histidine nanofibers induced amyloid cross-seeding reactions in several proteins and peptides including pathogenic Aβ 1−42 and brain extract components. Further, the histidine nanofibers exhibited oxidase activity and enhanced the oxidation of neurotransmitters. Cell-based studies confirmed the cellular internalization of histidine nanofibers in SH-SY5Y cells and subsequent cytotoxic effects through necrosis and apoptosis-mediated cell death. Since several complications including behavioral abnormality, developmental delay, and neurological disabilities are directly linked to abnormal accumulation of histidine, our findings provide a foundational understanding of the mechanism of histidine-related complications. Further, the ability of histidine nanofibers to catalyze amyloid seeding and oxidation reactions is equally important for both biological and materials science research.

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Section: ■ Discussionmentioning

confidence: 98%

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities

Prajapati,

Mittal,

Ansari

et al. 2024

ACS Appl. Mater. Interfaces

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“…Co is an essential component of vitamin B 12 and is an environmental toxin. Zheng et al showed that mice exposed to Co develop age-related neurodegeneration [ 258 ].…”

Section: Essential Metals In Alzheimer’s Diseasementioning

confidence: 99%

Metals in Alzheimer’s Disease

et al. 2023

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The role of metals in the pathogenesis of Alzheimer’s disease (AD) is still debated. Although previous research has linked changes in essential metal homeostasis and exposure to environmental heavy metals to the pathogenesis of AD, more research is needed to determine the relationship between metals and AD. In this review, we included human studies that (1) compared the metal concentrations between AD patients and healthy controls, (2) correlated concentrations of AD cerebrospinal fluid (CSF) biomarkers with metal concentrations, and (3) used Mendelian randomization (MR) to assess the potential metal contributions to AD risk. Although many studies have examined various metals in dementia patients, understanding the dynamics of metals in these patients remains difficult due to considerable inconsistencies among the results of individual studies. The most consistent findings were for Zn and Cu, with most studies observing a decrease in Zn levels and an increase in Cu levels in AD patients. However, several studies found no such relation. Because few studies have compared metal levels with biomarker levels in the CSF of AD patients, more research of this type is required. Given that MR is revolutionizing epidemiologic research, additional MR studies that include participants from diverse ethnic backgrounds to assess the causal relationship between metals and AD risk are critical.

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“…Oxidation at Cys113 inhibits Pin1 catalytic activity, promoting cis P‐tau accumulation as well (Chen et al, 2015). In addition, cobalt causes neurodegeneration via reducing Pin1 expression and consequently altering Pin1 substrates, including P‐tau, APP, Aβ, and GSK3β (Zheng et al, 2021). MiR‐140‐5p inhibitor enhances Pin1 expression and ameliorates Aβ induced learning and memory deficits (Khodabakhsh et al, 2022).…”

Section: Regulation Of Pin1mentioning

confidence: 99%

Function and regulation of cis P‐tau in the pathogenesis and treatment of conventional and nonconventional tauopathies

Wang,

Lu,

Zhou

2023

Journal of Neurochemistry

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Conventional tauopathies are a group of disease characterized by tau inclusions in the brains, including Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and certain types of frontotemporal dementia (FTD), among which AD is the most prevalent. Extensive post‐translational modifications, especially hyperphosphorylation, and abnormal aggregation of tau protein underlie tauopathy. Cis–trans isomerization of protein plays an important role in protein folding, function, and degradation, which is regulated by peptidyl‐proline isomerases (PPIases). Peptidyl‐prolyl cis–trans isomerase NIMA‐interacting 1 (Pin1), the only PPIase found to isomerize Pro following phosphorylated Ser or Thr residues, alters phosphorylated tau protein conformation at pT231‐P motif. The cis P‐tau but not trans P‐tau serves as an early driver of multiple neurodegenerative disease, encompassing AD, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), and vascular contributions to cognitive impairment and dementia (VCID). Cis but not trans P‐tau is resistant to protein dephosphorylation and degradation, and also prone to protein aggregation. Cis P‐tau loses its ability to stabilize microtubule, causing and spreading tauopathy mainly in axons, a pathological process called cistauosis. The conformation‐specific monoclonal antibody that targets only the cis P‐tau serves as a very early diagnosis method and a potential treatment of not only conventional tauopathies but also nonconventional tauopathies such as VCID, with clinical trials ongoing. Notably, cis P‐tau antibody is the only clinical‐stage Alzheimer's therapeutic that has shown the efficacy in animal models of not only AD but also TBI and stroke, which are very early stages of dementia. Here we review the identification and pathological consequences of cis pt231‐tau, the role of its regulator Pin1, as well as the clinical implication of cis pt231‐tau conformation‐specific antibody in conventional and nonconventional tauopathies.image

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Cobalt induces neurodegenerative damages through Pin1 inactivation in mice and human neuroglioma cells

Cited by 34 publications

References 58 publications

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities

Metals in Alzheimer’s Disease

Function and regulation of cis P‐tau in the pathogenesis and treatment of conventional and nonconventional tauopathies

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