Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

Multiple viral pathogens can pose a significant health risk to individuals. As a recent example, the β-coronavirus family virion, SARS-CoV-2, has quickly evolved as a pandemic leading to coronavirus disease 2019 (COVID-19) and has been declared by the World Health Organization as a Public Health Emergency of International Concern. To date, no definitive treatment or vaccine application exists for COVID-19. Although new investigations seek to repurpose existing antiviral treatments for COVID-19, innovative treatment strategies not normally considered to have antiviral capabilities may be critical to address this global concern. One such avenue that may prove to be exceedingly fruitful and offer exciting potential as new antiviral therapy involves the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), and AMP activated protein kinase (AMPK). Recent work has shown that mTOR pathways in conjunction with AMPK may offer valuable targets to control cell injury, oxidative stress, mitochondrial dysfunction, and the onset of hyperinflammation, a significant disability associated with COVID-19. Furthermore, pathways that can activate mTOR may be necessary for anti-hepatitis C activity, reduction of influenza A virus replication, and vital for type-1 interferon responses with influenza vaccination. Yet, important considerations for the development of safe and effective antiviral therapy with mTOR pathways exist. Under some conditions, mTOR can act as a double edge sword and participate in virion replication and virion release from cells. Future work with mTOR as a potential antiviral target is highly warranted and with a greater understanding of this novel pathway, new treatments against several viral pathogens may successfully emerge.

The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment

Parkinson's disease (PD) occurs in approximately 1% of the population over 65 years of age and has become increasingly more common with advances in age. The number of individuals older than 60 years has been increasing in modern societies, as well as life expectancy in developing countries; therefore, PD may pose an impact on the economic, social, and health structures of these countries. Oxidative stress is highlighted as an important factor in the genesis of PD, involving several enzymes and signaling molecules in the underlying mechanisms of the disease. This review presents updated data on the involvement of oxidative stress in the disease, as well as the use of antioxidant supplements in its therapy.

/pdf/oxidative-stress-in-parkinson-s-disease-potential-benefits-1viwl9zk2i.pdf

Oxidative Stress in Parkinson's Disease: Potential Benefits of Antioxidant Supplementation.

Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1.

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies.

Parkinson’s disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson’s disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson’s disease cell model. MPP+ was used to induce PD models in PC12 cells and classified into control, M0 (MPP+), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR. We showed that glutamine suppressed cytotoxicity induced by MPP+ in PC12 cells. MPP+ decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP+ increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1. These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP+ through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.

/pdf/glutamine-protects-against-oxidative-stress-injury-through-qownvmpuyt.pdf

Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

Substantial evidence indicates that microRNAs (miRNAs) can be used as biological markers of Parkinson's disease (PD) and contribute to the risk assessment, early diagnosis, and treatment. We aimed to explore the role and potential mechanism of miR-20a-5p on inflammation and oxidative stress in 1-methyl-4-phenyl pyridine ion- (MPP+-) induced HT22 cells. HT22 cells were pretreated with miR-20a-5p mimic and/or pcDNA-IRF9 for 24 h and then treated with MPP+ (0.5 mM) for 24 h. The cell viability and apoptosis were determined using the Cell Counting Kit-8 (CCK-8) and Annexin V FITC/PI staining flow cytometry assay, respectively. The expression and secretion of inflammatory factors and oxidative stress-related factors were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression levels were detected using Western blot analysis. Here, we discovered that MPP+ led to mitochondrial dysfunction, inflammation, and cell damage of HT22 cells, which were alleviated by miR-20a-5p overexpression. We further clarified that interferon regulatory factor 9 (IRF9) was a target gene of miR-20a-5p. IRF9 contributed to MPP+-induced mitochondrial disruption, inflammation, and cell apoptosis. Moreover, IRF9 hindered the improvement of miR-20a-5p overexpression on MPP+-induced neurotoxicity. Furthermore, the decrease of p-P65 level induced by miR-20a-5p mimic was significantly reversed by IRF9 overexpression. These findings demonstrate that miR-20a-5p contributes to MPP+-induced mitochondrial disruption and cell damage, and miR-20a-5p might be a novel therapeutic target for PD.

/pdf/mir-20a-5p-regulates-mpp-induced-oxidative-stress-and-2wfulsyyjd.pdf

Yingqian Zhao

Papers

Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

MiR-20a-5p Regulates MPP+-Induced Oxidative Stress and Neuroinflammation in HT22 Cells by Targeting IRF9/NF-κB Axis.