Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases

Zhang, Hui-Liang; Wang, Xiaochuan; R, Liu

doi:10.3390/biom12060785

Cited by 4 publications

(3 citation statements)

References 158 publications

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“…Furthermore, the quantity of zinc transporters decreases as the disease progresses, correlating to increased disease severity and cognitive impairment. It is unclear whether zinc concentrations or zinc transporters are the ultimate cause of AD [84,85].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Some studies have found lower serum zinc levels in PD patients [90,91], while others have found higher serum zinc levels. Studies reveal that methamphetamine causes dopaminergic cell death by generating reactive oxygen species and increasing the total amount of α-synuclein, a key element of Lewy bodies [85]. Zinc pretreatment reverses the aforementioned phenomena by increasing metallothionein expression in vitro, attenuating the accumulation of ROS in neurons [92,93].…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Contrastingly, numerous studies have demonstrated the detrimental effects of an aberrant accumula-tion of zinc in the substantia nigra and striatum, leading to dopaminergic neuronal cell death [88,94]. These findings are reinforced by the observation of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neuronal cell death in mice when zinc is pretreated [85]. In principle, these research findings imply that zinc dyshomeostasis may harbor dual involvement in the pathogenesis of PD contingent on zinc-modulated signaling pathways at specific stages of the disease.…”

Section: Parkinson's Diseasementioning

confidence: 99%

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The Role of Zinc in Modulating Acid-Sensing Ion Channel Function

Sun

Vijayalingam

et al. 2023

Biomolecules

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Acid-sensing ion channels (ASICs) are proton-gated, voltage-independent sodium channels widely expressed throughout the central and peripheral nervous systems. They are involved in synaptic plasticity, learning/memory, fear conditioning and pain. Zinc, an important trace metal in the body, contributes to numerous physiological functions, with neurotransmission being of note. Zinc has been implicated in the modulation of ASICs by binding to specific sites on these channels and exerting either stimulatory or inhibitory effects depending on the ASIC subtype. ASICs have been linked to several neurological and psychological disorders, such as Alzheimer’s disease, Parkinson’s disease, ischemic stroke, epilepsy and cocaine addiction. Different ASIC isoforms contribute to the persistence of each of these neurological and psychological disorders. It is critical to understand how various zinc concentrations can modulate specific ASIC subtypes and how zinc regulation of ASICs can contribute to neurological and psychological diseases. This review elucidates zinc’s structural interactions with ASICs and discusses the potential therapeutic implications zinc may have on neurological and psychological diseases through targeting ASICs.

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Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

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The Role of Zinc in Modulating Acid-Sensing Ion Channel Function

Sun

Vijayalingam

et al. 2023

Biomolecules

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Brain transcriptomic signatures for mood disorders and suicide phenotypes: an anterior insula and subgenual ACC network postmortem study

Arasappan,

Spears,

Shah

et al. 2024

Preprint

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Maintaining a balanced mood state is necessary for human well-being and survival. Several brain changes, including reduced anatomical integrity identified in imaging studies and molecular measures of transcriptomic changes identified in postmortem brain RNA-sequencing (RNA-Seq) studies, have been found in major depressive disorder (MDD) and bipolar disorder (BD) (here referred to as mood disorders). Although the human anterior insula (Ant-Ins) and subgenual anterior cingulate (sgACC) are involved in the regulation of mood/affect, and feeling states, studies dissecting the molecular neurobiological mechanisms of mood (dys)functions have not consistently targeted this critical brain network. Here, we studied the postmortem Ant-Ins and sgACC and applied whole-tissue RNA-seq measures of differentially expressed genes (DEGs) in mood disorders versus (vs.) psychiatrically unaffected controls (controls). We identified DEGs associated with mood disorder-related diagnostic phenotypes by combining gene co-expression, differential gene expression, and pathway-enrichment analyses. Using factor analysis of the postmortem phenotypic variables to determine relevant sources of population variances, we identified downregulation/under expression of inflammatory and protein synthesis-related genes associated with psychiatric morbidity (i.e., all co-occurring mental disorders and suicide outcomes/death by suicide) in Ant-Ins, in contrasts to upregulation of synaptic membrane and ion channel-related genes with increased psychiatric morbidity in sgACC. We further identified a preponderance of downregulated metabolic, protein synthesis, inflammatory, and synaptic membrane DEGs associated with suicide outcomes in relation to a factor representing longevity in the Ant-Ins and sgACC network. Our findings revealed a critical brain network molecular repertoire for mood disorder phenotypes, including suicide outcomes and longevity. This work provides a framework for studying directionally defined (downregulated vs. upregulated) molecular mechanisms for mood disorder phenotypic complexity and disease outcomes.

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Molecular Role of Protein Phosphatases in Alzheimer’s and Other Neurodegenerative Diseases

Hassan,

Yasir,

Shahzadi

et al. 2024

Biomedicines

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Alzheimer’s disease (AD) is distinguished by the gradual loss of cognitive function, which is associated with neuronal loss and death. Accumulating evidence supports that protein phosphatases (PPs; PP1, PP2A, PP2B, PP4, PP5, PP6, and PP7) are directly linked with amyloid beta (Aβ) as well as the formation of the neurofibrillary tangles (NFTs) causing AD. Published data reported lower PP1 and PP2A activity in both gray and white matters in AD brains than in the controls, which clearly shows that dysfunctional phosphatases play a significant role in AD. Moreover, PP2A is also a major causing factor of AD through the deregulation of the tau protein. Here, we review recent advances on the role of protein phosphatases in the pathology of AD and other neurodegenerative diseases. A better understanding of this problem may lead to the development of phosphatase-targeted therapies for neurodegenerative disorders in the near future.

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Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases

Cited by 4 publications

References 158 publications

The Role of Zinc in Modulating Acid-Sensing Ion Channel Function

The Role of Zinc in Modulating Acid-Sensing Ion Channel Function

Brain transcriptomic signatures for mood disorders and suicide phenotypes: an anterior insula and subgenual ACC network postmortem study

Molecular Role of Protein Phosphatases in Alzheimer’s and Other Neurodegenerative Diseases

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