Parkinson's disease(PD)is the second most common neurodegenerative disease after Alzheimer's disease,with high morbidity and high disability rate.Since the early symptoms of PD are not typical and often similar to those of normal aging or other diseases.It is easy to missed diagnosis and misdiagnosis,which seriously affects the diagnosis and treatment of this disease and aggravetes the burden on the patients' life.MicroRNAs(miRNA)are a class of endogenous non-coding RNAs that are involved in post-transcriptional regulation by binding to target messenger RNAs(mRNA).They are highly conserved,short,easy to obtain,and can stably exist in peripheral body fluids.They have been used as biomarkers for a variety of diseases.Recent studies have demonstrated that miRNA play an important role in the development of PD.This paper reviews the recent research progress of miR-7/124/155,three mature miRNA in PD,aiming to provide reference for clarifying the pathogenesis and guiding the diagnosis and treatment of PD.
Humans ; Parkinson Disease ; Neurodegenerative Diseases ; MicroRNAs/genetics* ; Gene Expression Regulation ; Biomarkers/metabolism*

This study aims to explore the neuroprotective mechanism of ginsenoside Re(GS-Re) on drosophila model of Parkinson's disease(PD) induced by rotenone(Rot). To be specific, Rot was used to induce PD in drosophilas. Then the drosophilas were grouped and respectively treated(GS-Re: 0.1, 0.4, 1.6 mmol·L~(-1); L-dopa: 80 μmol·L~(-1)). Life span and crawling ability of drosophilas were determined. The brain antioxidant activity [content of catalase(CAT), malondialdehyde(MDA), reactive oxygen species(ROS), superoxide dismutase(SOD)], dopamine(DA) content, and mitochondrial function [content of adenosine triphosphate(ATP), NADH:ubiquinone oxidoreductase subunit B8(NDUFB8) Ⅰ activity, succinate dehydrogenase complex, subunit B(SDHB) Ⅱ activity] were detected by enzyme-linked immunosorbent assay(ELISA). The number of DA neurons in the brains of drosophilas was measured with the immunofluorescence method. The levels of NDUFB8 Ⅰ, SDHB Ⅱ, cytochrome C(Cyt C), nuclear factor-E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), B-cell lymphoma/leukemia 2(Bcl-2)/Bcl-2-assaciated X protein(Bax), and cleaved caspase-3/caspase-3 in the brain were detected by Western blot. The results showed that model group [475 μmol·L~(-1) Rot(IC_(50))] demonstrated significantly low survival rate, obvious dyskinesia, small number of neurons and low DA content in the brain, high ROS level and MDA content, low content of SOD and CAT, significantly low ATP content, NDUFB8 Ⅰ activity, and SDHB Ⅱ activity, significantly low expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax, large amount of Cyt C released from mitochondria to cytoplasm, low nuclear transfer of Nrf2, and significantly high expression of cleaved caspase-3/caspase-3 compared with the control group. GS-Re(0.1, 0.4, and 1.6 mmol·L~(-1)) significantly improved the survival rate of PD drosophilas, alleviated the dyskinesia, increased DA content, reduced the loss of DA neurons, ROS level, and MDA content in brain, improved content of SOD and CAT and antioxidant activity in brain, maintained mitochondrial homeostasis(significantly increased ATP content and activity of NDUFB8 Ⅰ and SDHB Ⅱ, significantly up-regulated expression of NDUFB8 Ⅰ, SDHB Ⅱ, and Bcl-2/Bax), significantly reduced the expression of Cyt C, increased the nuclear transfer of Nrf2, and down-regulated the expression of cleaved caspase-3/caspase-3. In conclusion, GS-Re can significantly relieve the Rot-induced cerebral neurotoxicity in drosophilas. The mechanism may be that GS-Re activates Keap1-Nrf2-ARE signaling pathway by maintaining mitochondrial homeostasis, improves antioxidant capacity of brain neurons, then inhibits mitochondria-mediated caspase-3 signaling pathway, and the apoptosis of neuronal cells, thereby exerting the neuroprotective effect.
Animals ; Reactive Oxygen Species/metabolism* ; Antioxidants/pharmacology* ; Oxidative Stress ; NF-E2-Related Factor 2/metabolism* ; Caspase 3/metabolism* ; Parkinson Disease/genetics* ; bcl-2-Associated X Protein/metabolism* ; Neuroprotective Agents/pharmacology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Drosophila/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Apoptosis ; Superoxide Dismutase/metabolism* ; Adenosine Triphosphate/pharmacology*

Humans ; alpha-Synuclein/genetics* ; Parkinson Disease/pathology*

Humans ; Mitochondria/genetics* ; Mutation/genetics* ; Parkinson Disease/genetics* ; Protein Kinases ; Ubiquitin-Protein Ligases

Parkinson's disease (PD) is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta. The mutation of leucine-rich repeat kinase 2 (Lrrk2) is the most common autosomal dominant mutation in PD, and it has also been reported in sporadic cases. A growing body of research suggests that circadian rhythm disruption, particularly sleep-wake abnormality, is common during the early phase of PD. Our present study aimed to evaluate the impact of sleep deprivation (SD) on motor ability, sleep performance, and PD pathologies in Lrrk2^G2019S transgenic mice. After two months of SD, Lrrk2^G2019S mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits, a reduced striatal DA level, degenerated DAergic neurons, and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain. All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up. Moreover, a significant increase in α-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age. Taken together, our findings indicate that sleep abnormalities, as a risk factor, may contribute to the pathogenesis and progression of PD. Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.
Animals ; Electroencephalography ; Leucine/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Mice ; Mice, Transgenic ; Mutation ; Parkinson Disease/metabolism* ; Sleep Deprivation/complications* ; alpha-Synuclein/genetics*

In neuronal system, epigenetic modifications are essential for neuronal development, the fate determination of neural stem cells and neuronal function. The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease. Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington's disease. In the brain of Alzheimer's disease patients, the levels of H3K27ac and H3K9ac histone modifications increased. In addition, the alteration of RNA methylation in animal models of Alzheimer's disease and Parkinson's disease showed discrepancy trends. Therefore, epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases. Here, we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.
Animals ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Neurodegenerative Diseases/genetics* ; Parkinson Disease/genetics* ; Protein Processing, Post-Translational

Brain ; pathology ; Genome-Wide Association Study ; Humans ; Parkinson Disease ; genetics ; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases ; genetics ; Proto-Oncogene Proteins c-crk ; genetics

OBJECTIVE: To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family. METHODS: Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation. RESULTS: A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic. CONCLUSION Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.
Consanguinity ; Homozygote ; Humans ; Mutation, Missense ; Parkinson Disease ; genetics ; Pedigree ; Protein Deglycase DJ-1 ; genetics

OBJECTIVE: To report a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifesting as lumbago, hunchback and Parkinson's syndrome. METHODS: A 49-years-old male CADASIL patient was reported. Results of clinical examination, neuroimaging and genetic testing were analyzed. His family members were also subjected to genetic testing. Related literature was reviewed. RESULTS: The patient had no typical symptoms of CADASIL such as headache, repeated stroke, dementia and emotional disorders, but progressive Parkinson's syndrome, late onset lumbago, hunchback, dysphagia, and diplopia. Brain MRI showed left basal ganglia and external capsule lacunar infarction. Genetic testing revealed a point mutation c.1630C>T (p.R544C) in exon 11 of the NOTCH3 gene. A heterozygous mutation was detected in the same gene in his mother, elder sister and younger brother, all of whom showed different clinical phenotypes. CONCLUSION The clinical features of CADASIL are heterogeneous. Lumbago, humpback, and Parkinson's syndrome may be a rare clinical phenotype of CADASIL.
CADASIL ; complications ; genetics ; Humans ; Low Back Pain ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; Parkinson Disease ; etiology ; Receptor, Notch3 ; genetics

To investigate the effect of Parkinson's disease related protein DJ-1 on the cell proliferation, apoptosis, invasion and migration in human osteosarcoma cells and the underlying molecular mechanisms. 
 Methods: The protein expression levels of DJ-1 were detected in human osteosarcoma cell lines (MG-63, Saos-2, and U2OS) and human osteoblast cell line hFOB1.19 with or without deficiency in phosphatase and tensin homolog deleted from chromosome 10 (PTEN) were detected by Western blot. Osteosarcoma cells were treated with DJ-1 siRNA, and then the protein expression levels of DJ-1 were detected by Western blot. Cell survival rate of osteosarcoma cells was detected by cell counting kit-8 (CCK-8) assay. Cell apoptosis of osteosarcoma cells was measured by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Cell invasive and migration ability of osteosarcoma cells were examined by transwell invasion and migration assay. 
 Results: Compared with that of human osteoblast cell line (hFOB1.19), the protein expression level of DJ-1 was significantly upregulated in human osteosarcoma cell lines (MG-63, Saos-2, and U2OS) (all P<0.05), and U2OS had the highest level of DJ-1 when compared with the other three cell lines (P<0.01). DJ-1 siRNA could significantly down-regulate the DJ-1 protein expression in U2OS cells, and also diminish the cell survival rate. Moreover, DJ-1 down-regulation of DJ-1 could promote cell apoptosis, suppress the ability of cell invasion and migration, and increase the PTEN protein expression level (all P<0.05). In addition, the protein expression level of PTEN was markedly up-regulated in human osteosarcoma cell lines when compared with that in the hFOB1.19 cells (P<0.05). 
 Conclusion: DJ-1 can promote the cell proliferation, inhibit cell apoptosis, and decrease the ability of cell invasion and migration, and the potential underlying mechanisms may be associated with the up-regulation of PTEN protein expression.
Apoptosis ; genetics ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Invasiveness ; genetics ; PTEN Phosphohydrolase ; genetics ; Parkinson Disease ; physiopathology ; Protein Deglycase DJ-1 ; genetics ; metabolism ; RNA, Small Interfering ; genetics