Neurobiology of Parkinson’s Disease

Morelli, Micaela; Pinna, Annalisa

doi:10.3390/ijms24129933

Cited by 3 publications

(2 citation statements)

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“…Parkinson’s disease (PD) is one of the most rapidly growing neurological disorders and is characterized by movement symptoms, such as rigidity, slowness, and tremor ( Emamzadeh and Surguchov, 2018 ; Armstrong and Okun, 2020 ; Morelli and Pinna, 2023 ). These motor symptoms are caused by the pathological conditions of dopaminergic neurons in the substantia nigra (SN), which includes α-synuclein (SNCA) aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, and neuroinflammation ( Surmeier, 2018 ; Dong-Chen et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Chun,

Kim

2024

Front. Aging Neurosci.

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IntroductionParkinson’s disease (PD) is a rapidly growing neurological disorder characterized by diverse movement symptoms. However, the underlying causes have not been clearly identified, and accurate diagnosis is challenging. This study aimed to identify potential biomarkers suitable for PD diagnosis and present an integrative perspective on the disease.MethodsWe screened the GSE7621, GSE8397-GPL96, GSE8397-GPL97, GSE20163, and GSE20164 datasets in the NCBI GEO database to identify differentially expressed (DE) mRNAs in the substantia nigra (SN). We also screened the GSE160299 dataset from the NCBI GEO database to identify DE lncRNAs and miRNAs in plasma. We then constructed 2 lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) regulatory networks based on the ceRNA hypothesis. To understand the biological function, we performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses for each ceRNA network. The receiver operating characteristic analyses (ROC) was used to assess ceRNA results.ResultsWe identified 7 upregulated and 29 downregulated mRNAs as common DE mRNAs in the 5 SN datasets. In the blood dataset, we identified 31 DE miRNAs (9 upregulated and 22 downregulated) and 332 DE lncRNAs (69 upregulated and 263 downregulated). Based on the determined interactions, 5 genes (P2RX7, HSPA1, SLCO4A1, RAD52, and SIRT4) appeared to be upregulated as a result of 10 lncRNAs sponging 4 miRNAs (miR-411, miR-1193, miR-301b, and miR-514a-2/3). Competing with 9 genes (ANK1, CBLN1, RGS4, SLC6A3, SYNGR3, VSNL1, DDC, KCNJ6, and SV2C) for miR-671, a total of 26 lncRNAs seemed to function as ceRNAs, influencing genes to be downregulated.DiscussionIn this study, we successfully constructed 2 novel ceRNA regulatory networks in patients with PD, including 36 lncRNAs, 5 miRNAs, and 14 mRNAs. Our results suggest that these plasma lncRNAs are involved in the pathogenesis of PD by sponging miRNAs and regulating gene expression in the SN of the brain. We propose that the upregulated and downregulated lncRNA-mediated ceRNA networks represent mechanisms of neuroinflammation and dopamine neurotransmission, respectively. Our ceRNA network, which was associated with PD, suggests the potential use of DE miRNAs and lncRNAs as body fluid diagnostic biomarkers. These findings provide an integrated view of the mechanisms underlying gene regulation and interactions in PD.

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Section: Introductionmentioning

confidence: 99%

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Chun,

Kim

2024

Front. Aging Neurosci.

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“…The possible therapeutic use of selegiline was obscure until the mid-seventies, when it became evident that the drug exerts an L-dopa-sparing effect in Parkinson's disease therapy [2,3]. From this point of view, it was an essential finding that dopamine, the major neurotransmitter that is lost in the parkinsonian extrapyramidal system [4], is the substrate for MAO-B in humans [5]. Although selegiline became a standard element of the treatment of Parkinson's disease, pitfalls of the drug arose when its metabolism was investigated, leading to the demonstration that L-methamphetamine and L-amphetamine are among the metabolites [6].…”

Section: Introductionmentioning

confidence: 99%

Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline

Harsing,

Timar,

Miklya

2023

IJMS

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Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson’s disease. In their clinical application, however, differences in L-dopa-sparing potencies have been observed. The aim of this study was to find neurochemical and behavioral explanations for the antiparkinsonian effects of these drugs. We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [3H]dopamine release without influencing the resting [3H]dopamine release from rat striatal slices in 10−10–10−9 mol/L concentrations. Rasagiline added in 10−13 to 10−5 mol/L concentrations did not alter the resting or electrically stimulated [3H]dopamine release. Rasagiline (10−9 mol/L), however, suspended the stimulatory effect of selegiline on the electrically induced [3H]dopamine release. The trace amine-associated receptor 1 (TAAR1) antagonist EPPTB (10−8–10−7 mol/L) also inhibited the stimulatory effect of selegiline on [3H]dopamine release. The effect of selegiline in its enhancer dose (5.33 nmol/kg) against tetrabenazine-induced learning deficit measured in a shuttle box apparatus was abolished by a 5.84 nmol/kg dose of rasagiline. The selegiline metabolite (−)methamphetamine (10−9 mol/L) also exhibited enhancer activity on [3H]dopamine release. We have concluded that selegiline acts as an MAO-B inhibitor and a dopaminergic enhancer drug, and the latter relates to an agonist effect on TAAR1. In contrast, rasagiline is devoid of enhancer activity but may act as an antagonist on TAAR1.

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Definition of Neurobiology of Cancer

Mravec

2024

Neurobiology of Cancer

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Neurobiology of Parkinson’s Disease

Abstract: Parkinson’s disease (PD) is one of the most rapidly growing neurological disorders [...]

Cited by 3 publications

References 15 publications

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline

Definition of Neurobiology of Cancer

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