scholarly journals Celastrol Inhibits Dopaminergic Neuronal Death of Parkinson’s Disease through Activating Mitophagy

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 37 ◽  
Author(s):  
Ming-Wei Lin ◽  
Chi Chien Lin ◽  
Yi-Hung Chen ◽  
Han-Bin Yang ◽  
Shih-Ya Hung
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neuronal Death ◽  
Neuronal Apoptosis ◽  
Cell Model ◽  
Protein Accumulation ◽  
Motor Symptoms ◽  
Abnormal Protein ◽  
Mitochondrial Membrane Depolarization

Parkinson’s disease (PD) is a neurodegenerative disease, which is associated with mitochondrial dysfunction and abnormal protein accumulation. No treatment can stop or slow PD. Autophagy inhibits neuronal death by removing damaged mitochondria and abnormal protein aggregations. Celastrol is a triterpene with antioxidant and anti-inflammatory effects. Up until now, no reports have shown that celastrol improves PD motor symptoms. In this study, we used PD cell and mouse models to evaluate the therapeutic efficacy and mechanism of celastrol. In the substantia nigra, we found lower levels of autophagic activity in patients with sporadic PD as compared to healthy controls. In neurons, celastrol enhances autophagy, autophagosome biogenesis (Beclin 1↑, Ambra1↑, Vps34↑, Atg7↑, Atg12↑, and LC3-II↑), and mitophagy (PINK1↑, DJ-1↑, and LRRK2↓), and these might be associated with MPAK signaling pathways. In the PD cell model, celastrol reduces MPP+-induced dopaminergic neuronal death, mitochondrial membrane depolarization, and ATP reduction. In the PD mouse model, celastrol suppresses motor symptoms and neurodegeneration in the substantia nigra and striatum and enhances mitophagy (PINK1↑ and DJ-1↑) in the striatum. Using MPP+ to induce mitochondrial damage in neurons, we found celastrol controls mitochondrial quality by sequestering impaired mitochondria into autophagosomes for degradation. This is the first report to show that celastrol exerts neuroprotection in PD by activating mitophagy to degrade impaired mitochondria and further inhibit dopaminergic neuronal apoptosis. Celastrol may help to prevent and treat PD.

scholarly journals Review of prodromal symptoms in Parkinson's Disease detected by MRI, EEG And microbiome

2019 ◽  
Author(s):  
Isabel Cristina Echeverri ◽  
Maria de la Iglesia Vayá ◽  
Jose Molina Mateo ◽  
Francia Restrepo de Mejia ◽  
Belarmino Segura Giraldo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Evidence Synthesis ◽  
Magnetic Resonance Images ◽  
Event Related Potential ◽  
Motor Symptoms ◽  
The Brain ◽  
Early Parkinson’S Disease

Context: Parkinson’s disease (PD) is catalogued as a disorder that causes motor symptoms; the evidence of literature shows the PD starts with non-motor signs, which can be detected in prodromal phases. These previous phases can be analyzed and studied through magnetic resonance images (MRI), electroencephalography (EEG) and microbiome.Objective: To systematically review the areas of the brain and brain-gut axis which affect in early Parkinson’s disease that can possibly be visualized and analyzed by MRI, EEG and the microbiome.Evidence acquisition: Pubmed and Embase databases were used until July 30, 2018 as to search for early Parkinson’s disease at its earliest non-motor symptoms stage by using MRI, EEG, and microbiome. The search was performed according to the requirements of a systematic review. In order to identify reports, we evaluated them following the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Evidence synthesis: MRI and EEG have provided the advances to find features for PD over the last decade. Those techniques identify motor symptoms on substantia nigra where the patient shows a dopamine deficiency. However, over recent years, researchers have found that PD has prodromal phases, that is, PD is not simply a neurodegenerative disorder characterized by the dysfunction of dopaminergic. Thus, high field MRI, event-related potential (ERP) and microbiota data shows a significant change on the brain cortex, white and grey matter, the extrapyramidal system, brain signals and the gut.Conclusion: The structural MRI is a useful technique in detecting the stages of motor symptoms on the substantia nigra in patients with PD. The use of magnetic resonance as an early detector requires a high magnetic field, as to identify the areas which diagnose that the patient could be in the premotor stages. On the other hand, EEG performed well in detecting PD features. Furthermore, microbiome sequencing might include the classification of bacterial families that could help to detect PD in its prodromal phase. Thus, the combination of all these techniques can support the possibility of diagnosing PD in its very early stages.

scholarly journals Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson’s disease: a Chinese population-based study

2019 ◽  
Vol 41 (3) ◽  
pp. 661-667 ◽  
Author(s):  
Ting Li ◽  
Jing Shi ◽  
Bin Qin ◽  
Dongsheng Fan ◽  
Na Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Odds Ratio ◽  
Rating Scales ◽  
Binary Logistic Regression Analysis ◽  
Motor Symptoms ◽  
Visual Hallucinations ◽  
Roc Curve Analysis ◽  
Non Motor Symptoms

AbstractAs a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson’s Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson’s disease. Increased SN echogenicity is correlated with VH in Parkinson’s disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

scholarly journals Differential Effects of Dopaminergic Therapies on Dorsal and Ventral Striatum in Parkinson's Disease: Implications for Cognitive Function

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Penny A. MacDonald ◽  
Oury Monchi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Function ◽  
Substantia Nigra ◽  
Ventral Striatum ◽  
Functional Neuroimaging ◽  
Dorsal Striatum ◽  
Cell Loss ◽  
Motor Symptoms ◽  
Dopaminergic Therapy

Cognitive abnormalities are a feature of Parkinson's disease (PD). Unlike motor symptoms that are clearly improved by dopaminergic therapy, the effect of dopamine replacement on cognition seems paradoxical. Some cognitive functions are improved whereas others are unaltered or even hindered. Our aim was to understand the effect of dopamine replacement therapy on various aspects of cognition. Whereas dorsal striatum receives dopamine input from the substantia nigra (SN), ventral striatum is innervated by dopamine-producing cells in the ventral tegmental area (VTA). In PD, degeneration of SN is substantially greater than cell loss in VTA and hence dopamine-deficiency is significantly greater in dorsal compared to ventral striatum. We suggest that dopamine supplementation improves functions mediated by dorsal striatum and impairs, or heightens to a pathological degree, operations ascribed to ventral striatum. We consider the extant literature in light of this principle. We also survey the effect of dopamine replacement on functional neuroimaging in PD relating the findings to this framework. This paper highlights the fact that currently, titration of therapy in PD is geared to optimizing dorsal striatum-mediated motor symptoms, at the expense of ventral striatum operations. Increased awareness of contrasting effects of dopamine replacement on dorsal versus ventral striatum functions will lead clinicians to survey a broader range of symptoms in determining optimal therapy, taking into account both those aspects of cognition that will be helped versus those that will be hindered by dopaminergic treatment.

scholarly journals LncRNA SOX2-OT Participates in Parkinson’s Disease Through Regulating miRNA-942-5p/NAIF1 Axis

2021 ◽  
Author(s):  
Yabi Guo ◽  
Yanyang Liu ◽  
Hong Wang ◽  
Peijun Liu
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Apoptosis ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Sod Activity ◽  
Software Analysis ◽  
Direct Target

Abstract Parkinson’s disease (PD) is a neurodegenerative disease. Studies have shown that lncRNA SOX2-OT was highly expressed in PD patients, but its specific functions and mechanisms still need further research. This study aimed to explore whether lncRNA SOX2-OT could regulate oxidative stress, inflammation and neuronal apoptosis in PD in vitro model and explored the underlying mechanism. An in vitro PD cell model was induced by 1-methyl-4-phenylpyridinium (MPP+). The results of the biological software analysis and luciferase reporter assay indicated that miR-942-5p was a direct target of lncRNA SOX2-OT, and NAIF1 was a direct target of miR-942-5p. Experiments showed that the expression levels of lncRNA SOX2-OT and NAIF1 were increased, and miR-942-5p expression was decreased in SH-SY5Y cells following MPP+ treatment. In addition, MPP+ treatment reduced SH-SY5Y cell viability, induced apoptosis, increased cleaved-Caspase3 protein expression, and increased cleaved-Caspase3/Caspase3 ratio, increased LDH viability, and increased the levels of TNF-α, IL-1β and ROS in SH-SY5Y cells, reduced SOD activity, however, all these effects were inhibited by SOX2-OT-siRNA, and these inhibitions were reversed by miR-942-5p inhibitor. Moreover, the protective role of miR-942-5p mimic in MPP+ induced SH-SY5Y cells was significantly eliminated by NAIF1-plasmid. In summary, this study confirmed that lncRNA SOX2-OT regulated oxidative stress, inflammation and neuronal apoptosis via directly regulating the miR-942-5p/NAIF1 signal axis, and then participated in the occurrence and development of PD. These data provide a new potential targets for PD diagnosis and treatment.

scholarly journals Microbiota and Parkinson's disease (overview)

2020 ◽  
pp. 10-14
Author(s):  
R. R. Tyutina ◽  
A. A. Pilipovich ◽  
V. L. Golubev ◽  
Al. B. Danilov
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Substantia Nigra ◽  
Subsequent Development ◽  
Alpha Synuclein ◽  
Intestinal Wall ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Parkinson's disease (PD) is characterized by both motor (hypokinesia, resting tremor, rigidity, postural instability) and non-motor symptoms. It is known that some non-motor manifestations, such as disturbances in smell, sleep, depression, gastrointestinal dysfunction, and others, may precede motor symptoms. Replenishment of dopamine deficiency, which, as known, develops in PD due to the death of dopaminergic neurons of the substantia nigra, makes it possible to influence most motor and some non-motor symptoms of parkinsonism, however many non-motor manifestations remain resistant to this therapy. In addition, it has only a symptomatic effect, and the pathogenetic treatment of PD is currently unavailable, which is primarily due to insufficient knowledge about the etiology and mechanisms of the development of the disease. In particular, it has already been established that alpha synuclein (a pathomorphological marker of PD) begins to be deposited in the intestinal wall, in the enteric nervous system (ENS) long before it appears in neurons of the substantia nigra. Understanding the mechanism of interaction along the axis “intestine – brain”, the role of intestinal wall dysfunction in the onset and development of PD can lead to the development of new directions in the treatment of this disease. Today, the role of microbiota, in particular the intestinal microbiota, in the functioning of the human body, its various systems, including the nervous system, is widely studied in the world. The influence of its imbalance on the activation of inflammatory reactions in the ENS and the possibility of the subsequent development of PD are considered. This review provides some evidence supporting the hypothesis that PD can be initiated in the gut. In addition, the possibilities of influencing the course of BP using pre-, pro-, syn- and metabiotics are considered.

scholarly journals The Pathogenesis of Parkinson's Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes?

2021 ◽  
Vol 12 ◽  
Author(s):  
Adina N. MacMahon Copas ◽  
Sarah F. McComish ◽  
Jean M. Fletcher ◽  
Maeve A. Caldwell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Substantia Nigra ◽  
Glial Cells ◽  
Immune Cells ◽  
Neuronal Cell ◽  
Substantia Nigra Pars Compacta ◽  
Motor Symptoms ◽  
Peripheral Immune Cells

Parkinson's disease (PD), the second most common neurodegenerative disease, is characterised by the motor symptoms of bradykinesia, rigidity and resting tremor and non-motor symptoms of sleep disturbances, constipation, and depression. Pathological hallmarks include neuroinflammation, degeneration of dopaminergic neurons in the substantia nigra pars compacta, and accumulation of misfolded α-synuclein proteins as intra-cytoplasmic Lewy bodies and neurites. Microglia and astrocytes are essential to maintaining homeostasis within the central nervous system (CNS), including providing protection through the process of gliosis. However, dysregulation of glial cells results in disruption of homeostasis leading to a chronic pro-inflammatory, deleterious environment, implicated in numerous CNS diseases. Recent evidence has demonstrated a role for peripheral immune cells, in particular T lymphocytes in the pathogenesis of PD. These cells infiltrate the CNS, and accumulate in the substantia nigra, where they secrete pro-inflammatory cytokines, stimulate surrounding immune cells, and induce dopaminergic neuronal cell death. Indeed, a greater understanding of the integrated network of communication that exists between glial cells and peripheral immune cells may increase our understanding of disease pathogenesis and hence provide novel therapeutic approaches.

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