Identification of Altered Blood MicroRNAs and Plasma Proteins in a Rat Model of Parkinson’s Disease

Yadav, Sanjeev Kumar Singh; Pandey, Anuj Kumar; Sarkar, Sana; Parmar, Devendra; Yadav, Sanjay

doi:10.1007/s12035-021-02636-y

Cited by 12 publications

(12 citation statements)

References 54 publications

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“…Tuba1c is hypothesized to be a Parkin-dependent ubiquitylation target and interactor of Pink1 ( Rakovic et al, 2011 ; Zanon et al, 2013 ). Recent evidence has identified the dysregulation of Tuba1c as a potential biomarker of PD in a rotenone-induced rat model of PD ( Yadav et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats

Lechner

Welsch

Pahapill

et al. 2022

Front. Behav. Neurosci.

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Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochondrial dysfunction, exhibit early stage behavioral deficits, including vocal communication and anxiety, that progress during mid-to-late adulthood (6–12 months of age). Yet, the biological pathways and mechanisms that lead to prodromal dysfunction are not well understood. This study investigated the Pink1−/− rat in young adulthood (2 months of age). Mixed sex groups of Pink1−/− rats and wildtype (WT) controls were assayed for limb motor, anxiety, and vocal motor behaviors. A customized NanoString CodeSet, based on genetic work in later adulthood, was used to probe for the up regulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. In summary, the data show sex- and genotype-differences in limb motor, anxiety, and vocal motor behaviors. Specifically, female Pink1−/− rats demonstrate less anxiety-like behavior compared to male Pink1−/− rats and female rats show increased locomotor activity compared to male rats. Pink1−/− rats also demonstrate prodromal ultrasonic vocalization dysfunction across all acoustic parameters and sex differences were present for intensity (loudness) and peak frequency. These data demonstrate a difference in phenotype in the Pink1−/− model. Tuba1c transcript level was identified as a key marker negatively correlated to ultrasonic vocalization at 2 months of age. Identifying genes, such as Tuba1c, may help determine early predictors of PD pathology in the Pink1−/− rat and serve as targets for future drug therapy studies.

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Section: Discussionmentioning

confidence: 99%

Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats

Lechner

Welsch

Pahapill

et al. 2022

Front. Behav. Neurosci.

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“…It has been suggested that dysregulation of miRNA is involved in the pathogenesis of PD [104,105]. In 2018, Oh et al found that miR-221 was downregulated in both DJ-1 KD cells and murine brain tissue.…”

Section: Role Of Dj-1 In Apoptosismentioning

confidence: 99%

Pathogenesis of DJ-1/PARK7-Mediated Parkinson’s Disease

Skou,

Johansen,

Okarmus

et al. 2024

Cells

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Parkinson’s disease (PD) is a common movement disorder associated with the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Mutations in the PD-associated gene PARK7 alter the structure and function of the encoded protein DJ-1, and the resulting autosomal recessively inherited disease increases the risk of developing PD. DJ-1 was first discovered in 1997 as an oncogene and was associated with early-onset PD in 2003. Mutations in DJ-1 account for approximately 1% of all recessively inherited early-onset PD occurrences, and the functions of the protein have been studied extensively. In healthy subjects, DJ-1 acts as an antioxidant and oxidative stress sensor in several neuroprotective mechanisms. It is also involved in mitochondrial homeostasis, regulation of apoptosis, chaperone-mediated autophagy (CMA), and dopamine homeostasis by regulating various signaling pathways, transcription factors, and molecular chaperone functions. While DJ-1 protects neurons against damaging reactive oxygen species, neurotoxins, and mutant α-synuclein, mutations in the protein may lead to inefficient neuroprotection and the progression of PD. As current therapies treat only the symptoms of PD, the development of therapies that directly inhibit oxidative stress-induced neuronal cell death is critical. DJ-1 has been proposed as a potential therapeutic target, while oxidized DJ-1 could operate as a biomarker for PD. In this paper, we review the role of DJ-1 in the pathogenesis of PD by highlighting some of its key neuroprotective functions and the consequences of its dysfunction.

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“…Label-Free Quantitative LC-MS/MS Proteomics Label-Free quanti cation have been performed as described in our earlier lab studies [21][22][23]. In brief, protein was isolated from SH-SY5Y and HMC3 cells and quanti ed using Pierce bicinchoninic acid (BCA) protein assay kit (Catalogue 23,227).…”

Section: Openarray Technology Based On Real-time Pcr Of Mirnamentioning

confidence: 99%

Crosstalk Between miRNA and Protein Expression Profiles in Nitrate-Exposed Brain Cells

et al. 2023

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Growing evidence reported a strong association between the ingestion of nitrate and adverse health consequences in humans, including its detrimental impact on the developing brain. The present study identi ed miRNAs and proteins in SH-SY5Y human neuroblastoma cells and HMC3 human microglial cells using high throughput techniques in response to nitrate level most prevalent in the environment (mainly India) (X) and an exceptionally high nitrate level (5X) that can be reached in the near future. Cells were exposed to mixtures of nitrates for 72 h at doses of X and 5X, 320 mg/L and 1600 mg/L, respectively. OpenArray and LCMS analysis revealed that maximum deregulation in miRNAs and proteins was found in cells exposed to 5X dose. Top deregulated miRNAs include miR-34b, miR-34c, miR-155, miR-143, and miR-145. The proteomic pro les of both cell types include proteins that are potential targets of deregulated miRNAs. These miRNAs and their targeted proteins are involved in multiple functions, including cellular senescence, cell cycle, apoptosis, neuronal disorders, brain development, and homeostasis. Further, measuring mitochondrial bioenergetics in cells exposed to nitrate using a Seahorse XFp ux analyzer revealed that a 5X dose causes a signi cant reduction in oxygen consumption rate (OCR) and other bioenergetics parameters in both cell types. In summary, our studies have demonstrated that 5X dose of nitrate signi cantly alters cellular physiology and functions by deregulating several miRNAs and proteins. However, X dose of nitrate that is most prevalent in the environment has not caused any adverse effects on any cell type.

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Identification of Altered Blood MicroRNAs and Plasma Proteins in a Rat Model of Parkinson’s Disease

Cited by 12 publications

References 54 publications

Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats

Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats

Pathogenesis of DJ-1/PARK7-Mediated Parkinson’s Disease

Crosstalk Between miRNA and Protein Expression Profiles in Nitrate-Exposed Brain Cells

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