Signature of Aberrantly Expressed microRNAs in the Striatum of Rotenone-Induced Parkinsonian Rats

Horst, Camila Hillesheim; Schlemmer, Franciele; Montenegro, Natália de Aguiar; Domingues, Ana Carolina Martins; Ferreira, Gabriel Ginani; Ribeiro, Cínthia Yara da Silva; Andrade, Rafael Rocha de; Del‐Bel, Elaine; Titze‐de‐Almeida, Simoneide Souza; Titze‐de‐Almeida, Ricardo

doi:10.1007/s11064-018-2638-0

Cited by 34 publications

(18 citation statements)

References 63 publications

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“…Consistent with these observations, profilin expression was reduced in the MP of psA30P mice. In line with our findings, miR-132-3p expression was increased in the striatum of a symptomatic rotenoneinduced PD rat model 76 .…”

Section: Discussionsupporting

confidence: 91%

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Gries

Christmann

Schulte

et al. 2020

Preprint

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Parkinson's disease (PD) usually has a late clinical onset. The lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use an -synuclein-overexpressing transgenic (Th-1-SNCA-A30P) mouse model of PD to identify appropriate candidate markers in the gut for early stages of PD before hallmark symptoms begin to manifest. A30P mice did not show alterations in gait parameters at 2 months of age, and these mice were therefore defined as pre-symptomatic A30P mice (psA30P). We discovered early functional motility changes in the gut and early molecular dysregulations in the myenteric plexus of psA30P mice by comparative protein and miRNA profiling and cell culture experiments. We found that the proteins neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are potential biomarkers of early PD that may facilitate timely treatment and/or prevention of PD in men.

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Section: Discussionsupporting

confidence: 91%

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Gries

Christmann

Schulte

et al. 2020

Preprint

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“…In the CNS, miR-26a was observed to be upregulated the SN tissues and in the exosomes isolated from the CSF of PD patients as compared to healthy controls [25,30]. In the striatal tissues of rodent PD models, miR-26a upregulation was observed in rotenone-treated rats [47] while miR-26b upregulation was reported in LRRK2-KO mice [28]. However, in the PBMCs isolated from PD patients, miR-26a downregulation was detected instead [31].…”

Section: The Biogenesis and Function Of Mirnasmentioning

confidence: 99%

Role of MicroRNAs in Parkinson’s Disease

Goh

Chao

Dheen

et al. 2019

IJMS

150

103

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Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.

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“…dysregulation of miR-34a-5p in the human brain thus far (62). However, some studies have reported the over-expression of miR-34a-5p both in in vitro and in vivo models of Pd, such as differentiated Pc12 cells treated with the dopaminergic neurotoxin MPP + and rats chronically exposed to rotenone (63)(64)(65), respectively. In addition, the downregulation of miR-34a-5p induced by lithium or the use of anti-miR molecules improved cell survival and showed neuroprotective effects in neuronal cells treated with Pd-associated neurotoxins (paraquat and rotenone) (66,67).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑34a‑5p expression in the plasma and in its extracellular vesicle fractions in subjects with Parkinson's disease: An exploratory study

et al. 2020

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Parkinson's disease (Pd) is an important disabling age-related disorder and is the second most common neurodegenerative disease. currently, no established molecular biomarkers exist for the early diagnosis of Pd. circulating microRNAs (miRNAs), either vesicle-free or encapsulated in extracellular vesicles (EVs), have emerged as potential blood-based biomarkers also for neurodegenerative diseases. In this exploratory study, we focused on miR-34a-5p because of its well-documented involvement in neurobiology. To explore a differential profile of circulating miR-34a-5p in PD, Pd patients and age-matched control subjects were enrolled. Serial ultracentrifugation steps and density gradient were used to separate EV subpopulations from plasma according to their different sedimentation properties (Large, Medium, Small EVs). characterization of EV types was performed using western blotting and atomic force microscopy (AFM); purity from protein contaminants was checked with the colorimetric nanoplasmonic assay. circulating miR-34a-5p levels were evaluated using qPcR in plasma and in each EV type. miR-34a-5p was significantly up-regulated in small EVs devoid of exogenous protein contaminants (pure SEVs) from Pd patients and ROc analysis indicated a good diagnostic performance in discriminating patients from controls (AUc=0.74, P<0.05). Moreover, miR-34a-5p levels in pure SEVs were associated with disease duration, Hoehn and Yahr and Beck depression Inventory scores. These results underline the necessity to examine the miRNA content of each EV subpopulation to identify miRNA candidates with potential diagnostic value and lay the basis for future studies to validate the overexpression of circulating miR-34a-5p in Pd via the use of pure SEVs.

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Signature of Aberrantly Expressed microRNAs in the Striatum of Rotenone-Induced Parkinsonian Rats

Cited by 34 publications

References 63 publications

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Role of MicroRNAs in Parkinson’s Disease

MicroRNA‑34a‑5p expression in the plasma and in its extracellular vesicle fractions in subjects with Parkinson's disease: An exploratory study

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