RhoA Signaling in Neurodegenerative Diseases

Schmidt, Sissel Ida; Blaabjerg, Morten; Freude, Kristine; Meyer, Morten

doi:10.3390/cells11091520

Cited by 61 publications

(50 citation statements)

References 229 publications

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“…On the other hand, PKN plays a role in regulating tau phosphorylation. 31 The present study results show a significant effect of dose and pattern of ionizing irradiation on the elevation of p-tau in bone marrow cells. Li et al, 2014, 32 reported that ionizing radiation causes changes in tau phosphorylation in cultured cells, which may increase the risk of the development of Alzheimer's disease.…”

Section: Discussionsupporting

confidence: 56%

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats

2022

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Most studies of the biological effects of ionizing radiation have been done on a single acute dose, while clinically and environmentally exposures occur under chronic/repetitive conditions. It is important to study effects of different patterns of ionizing radiation. In this study, a rat model was used to compare the effects of repetitive and acute exposure. Groups: (I) control, (II, III) were exposed to fractionated doses (1.5 GyX4) and (2 GyX4), respectively/24h interval, and (IV, V) were exposed to 6 Gy and 8 Gy of whole-body gamma irradiation, respectively. The gene expression of MAPT and tau phosphorylation increased in all irradiated groups but the gene expression of PKN not affected. TGFβ% increased at dose of 2 GyX4 only. In addition, the cell cycle was arrested in S phase. Micronucleus (MN) increased and cell proliferation decreased. In conclusion, the dose and pattern of ionizing radiation do not affect the MAPT and PKN gene expression, but TGF-β, p-tau, MN assay and cell proliferation are significantly affected. The dose of 2 GyX4 showed distinctive effect. Repetitive exposure may increase TGF-β%, which causes radio-resistance and, G2/M delay. Thus, the cell cycle could be regulated in a different manner according to the dose and pattern of irradiation.

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Section: Discussionsupporting

confidence: 56%

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats

2022

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“…Based on the primary structure of RHOA isoforms, only the major isoform 1 (Ensembl ID: ENST00000418115) and isoform 2 (RHOAiso2, Ensembl ID: ENST00000422781) confer RhoA GTPase activity and are ubiquitously expressed in multiple normal and cancer tissues (Figure 2C and Supporting Information: Figure ). However, there are no functional and mechanistic studies of RHOAiso2 in the literature 31 …”

Section: Resultsmentioning

confidence: 99%

“…However, there are no functional and mechanistic studies of RHOAiso2 in the literature. 31 Third, the alternative spliced RHOAiso2 (UniProt ID: C9JX21) harbored an alternate 3′ coding exon with a unique Alu/SINE RNA sequence translated into a different C-terminal polypeptide and is likely to play some distinct biological functions compared to the major RHOA isoform 1 (UniProt ID: P61586) (Figure 2C and Supporting Information: Information: Figure 4B). Finally, RHOA GTPase activity behaves as a molecular switch to catalyze the exchange of guanosine diphosphate (GDP) for GTP to modulate the dynamic organization of the actin cytoskeleton in cell motility, neuronal growth polarity, and morphogenesis with implications in cancers and in human diseases such as the central nervous system (CNS), diabetic nephropathy, and hypertension.…”

mentioning

confidence: 99%

Somatic A‐to‐I RNA‐edited RHOA isoform 2 specific‐R176G mutation promotes tumor progression in lung adenocarcinoma

Chen

Huang

Shih

et al. 2022

Molecular Carcinogenesis

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Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY ® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3′ RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein

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“…RhoA signaling has been directly implicated in neurodegenerative diseases, including Alzheimer's disease (AD), Picks disease (PiD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS; Huesa et al, 2010;Aguilar et al, 2017;Schmidt et al, 2022). Dendritic spine loss, a hallmark of early neurodegeneration, is regulated by RhoA signaling.…”

Section: Involvement In Neurodegenerationmentioning

confidence: 99%

Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders

Akhtar

Bunner²,

Brennan³

et al. 2023

Front. Cell. Neurosci.

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Neurodegeneration is associated with defects in cytoskeletal dynamics and dysfunctions of the vesicular trafficking and sorting systems. In the last few decades, studies have demonstrated that the key regulators of cytoskeletal dynamics are proteins from the Rho family GTPases, meanwhile, the central hub for vesicle sorting and transport between target membranes is the Rab family of GTPases. In this regard, the role of Rho and Rab GTPases in the induction and maintenance of distinct functional and morphological neuronal domains (such as dendrites and axons) has been extensively studied. Several members belonging to these two families of proteins have been associated with many neurodegenerative disorders ranging from dementia to motor neuron degeneration. In this analysis, we attempt to present a brief review of the potential crosstalk between the Rab and Rho family members in neurodegenerative pathologies such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease, and amyotrophic lateral sclerosis (ALS).

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RhoA Signaling in Neurodegenerative Diseases

Cited by 61 publications

References 229 publications

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats

The Influence of Different γ-Irradiation Patterns on Factors that May Affect Cell Cycle Progression in Male Rats

Somatic A‐to‐I RNA‐edited RHOA isoform 2 specific‐R176G mutation promotes tumor progression in lung adenocarcinoma

Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders

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