Aquaporin 4: A key player in Parkinson's disease

Tamtaji, Omid Reza; Behnam, Mohammad; Pourattar, Mohammad Ali; Jafarpour, Hamed; Asemi, Zatollah

doi:10.1002/jcp.28871

Cited by 39 publications

(25 citation statements)

References 105 publications

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“…Additional genes associated with mechanisms implicated in PD pathogenesis are also differentially expressed in T cells from PD_R subjects, including septin 5 (Son et al, 2005), the GDNF receptor (Sandmark et al, 2018), monoamine oxidase S, aquaporin (Tamtaji et al, 2019), LAMP3 (Liu et al, 2011) which has also been associated with REM sleep disorder (a risk factor for PD (Mufti et al, 2021)), polo-like kinase 1 (Mbefo et al, 2010), and myeloperoxidase (Maki et al, 2019). Most of these genes have been found previously to be expressed in neurons, but here we show for the first time DE of these genes in peripheral cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

Dhanwani

Lima-Junior

Sethi

et al. 2021

Preprint

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Parkinson's disease (PD) is a multi-stage neurodegenerative disorder with largely unknown etiology. Recent findings have identified PD-associated autoimmune features including roles for T cells. To further characterize the role of T cells in PD, we performed RNA sequencing on PBMC and peripheral CD4 and CD8 memory T cell subsets derived from PD patients and age-matched healthy controls. When the groups were stratified by their T cell responsiveness to alpha-synuclein (α-syn) as a proxy for ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD associated gene signature. We identified a significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5 and CCR1. In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin. Together, these findings suggest that features of circulating T cells with α-syn-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets.

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Section: Discussionmentioning

confidence: 99%

Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

Dhanwani

Lima-Junior

Sethi

et al. 2021

Preprint

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“…AQP4 has been implicated in the pathophysiology of many neurological (23,(27)(28)(29)(30)(31)(32) and psychiatric (33)(34)(35) diseases. In a previous study, AQP4 gene polymorphisms were examined in children with febrile seizures and revealed no association with the rs1058424 AT genotype or rs3763043 CT genotype SNPs.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case–Control Study

Sytwu

Lung

2020

Front. Psychiatry

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Background: In psychiatric illness, pathogenic role of neuroinflammation has been supported by multiple lines of evidence. Astrocytes contribute to the blood-brain barrier (BBB) with formation of the "glymphatic" drainage system of the central nervous system (CNS) through perivascular processes. Found primarily at the end-feet of astrocytes, the aquaporin 4 (AQP4) gene has been suspected to play putative roles in the development of psychiatric disorders as well as the clearance of the glymphatic system. However, there remain many uncertainties because of the limited research on AQP4. The present study is focused on the association between AQP4 gene polymorphisms and schizophrenia (SCZ) in the Southern Chinese Han population. Methods: Two hundred ninety-two patients and 100 healthy controls were enrolled in this study. To study the relationship of AQP4 gene polymorphisms and SCZ, genetic information was drawn from a cohort of 100 healthy controls and 100 matched patients with SCZ of Southern Han Chinese descent. Comparisons of the allele and genotype distributions between control and case groups were made using the c2 test. Two-group comparisons were made to assess the linkage equilibrium and haplotype. Results: Three SNPs were found. In comparison to healthy controls, patients had higher T-allele frequencies at rs1058424 and G-allele frequencies at rs3763043 (p = 0.043 and p = 0.045, respectively). Furthermore, there is an association between the decreased risk of SCZ and the AA genotype at both rs1058424 (p = 0.021, OR = 2.04) and rs3763043 (p = 0.018, OR = 2.25) The TCG haplotype (p = 0.036) was associated with a potential risk of SCZ, while the ACA haplotype (p = 0.0007) was associated with a decreased risk of SCZ and retained statistical significance after Bonferroni correction (p = 0.006). Conclusions: An etiological reference for SCZ is provided by the association between AQP4 gene polymorphisms and SCZ in Southern Han Chinese population.

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“…In addition, the regulation of water permeability by astrocytic water channels, aquaporin-4 (AQP4), in the BBB plays an important role in several physiological conditions in the CNS. Recently, the expression and regulation of AQP4 have been studied in several pathological situations, suggesting that AQP4 participates in the onset and progression of PD [145]. Xue et al [146] reported that AQP4-deficient mice displayed significantly stronger microglial inflammatory responses and a markedly greater loss of dopaminergic neurons after MPTP injection.…”

Section: Astrocyte Dysfunction In Parkinsonismmentioning

confidence: 99%

Neuron-Astrocyte Interactions in Parkinson’s Disease

Miyazaki

Asanuma

2020

Cells

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. PD patients exhibit motor symptoms such as akinesia/bradykinesia, tremor, rigidity, and postural instability due to a loss of nigrostriatal dopaminergic neurons. Although the pathogenesis in sporadic PD remains unknown, there is a consensus on the involvement of non-neuronal cells in the progression of PD pathology. Astrocytes are the most numerous glial cells in the central nervous system. Normally, astrocytes protect neurons by releasing neurotrophic factors, producing antioxidants, and disposing of neuronal waste products. However, in pathological situations, astrocytes are known to produce inflammatory cytokines. In addition, various studies have reported that astrocyte dysfunction also leads to neurodegeneration in PD. In this article, we summarize the interaction of astrocytes and dopaminergic neurons, review the pathogenic role of astrocytes in PD, and discuss therapeutic strategies for the prevention of dopaminergic neurodegeneration. This review highlights neuron-astrocyte interaction as a target for the development of disease-modifying drugs for PD in the future.

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Aquaporin 4: A key player in Parkinson's disease

Cited by 39 publications

References 105 publications

Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

Transcriptional analysis of peripheral memory T cells reveals Parkinson’s disease-specific gene signatures

Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case–Control Study

Neuron-Astrocyte Interactions in Parkinson’s Disease

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