scholarly journals Insulin Sensitivity in De Novo Parkinson's Disease: A Hyperinsulinemic‐Euglycemic Clamp Study

2020 ◽  
Vol 35 (9) ◽  
pp. 1693-1694
Author(s):  
N. Ahmad Aziz ◽  
Raymund A.C. Roos ◽  
Hanno Pijl
2021 ◽  
Vol 331 ◽  
pp. e44-e45
Author(s):  
W. Wang ◽  
K. Willems Van Dijk ◽  
C.A. Wijsman ◽  
M.P. Rozing ◽  
S.P. Mooijaart ◽  
...  

Endocrine ◽  
2005 ◽  
Vol 27 (1) ◽  
pp. 011-016 ◽  
Author(s):  
Zeki Yesilova ◽  
Cagatay Oktenli ◽  
S. Yavuz Sanisoglu ◽  
Ugur Musabak ◽  
Erdinc Cakir ◽  
...  

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.


2018 ◽  
Author(s):  
Elena Moro ◽  
Emmanuelle Bellot ◽  
Sara Meoni ◽  
Pierre Pelissier ◽  
Ruxandra Hera ◽  
...  

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.


2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Benedict Tanudjojo ◽  
Samiha S. Shaikh ◽  
Alexis Fenyi ◽  
Luc Bousset ◽  
Devika Agarwal ◽  
...  

Abstractα-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons.


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