Sestrin2 as Serum Protein Marker and Potential Therapeutic Target for Parkinson’s Disease

2019 ◽  
Author(s):  
Nitish Rai ◽  
Ashish Datt Upadhyay ◽  
Vinay Goyal ◽  
Sadanand Dwivedi ◽  
Aparajit Ballav Dey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older Adult ◽  
Neuroblastoma Cells ◽  
Ethanolic Extract ◽  
Threshold Value ◽  
Syzygium Aromaticum ◽  
Protein Marker ◽  
Rescue Effect ◽  
Adult Control

Abstract Sestrin2 (Sesn2) appears to mediate neuroprotection against Parkinson’s disease (PD)-associated pathophysiology, however, the mechanism is unknown. This pilot study examines serum Sesn2 level in PD patients and older adult control and also interrogates the rescue effect of Syzygium aromaticum extract on the neurotoxicity by paraquat in neuroblastoma cells. The blood sample was collected from 36 PD patients and 54 older adult control and concentration of serum Sesn2 was measured by surface plasmon resonance and western blot. A significantly elevated level of Sesn2 (p < .0001) was observed in sera of PD group (15.96 ± 2.428 ng/μL) than the control (13.65 ± 2.125 ng/μL) which was further confirmed by western blotting. The receiver operating characteristic (ROC) curve (0.76) determined the threshold value of ≥14.58 ng/μL for differentiating PD from control. The S aromaticum extract exhibited the rescue effect from paraquat induced toxicity in SH-SY5Y cells. Further, these cells showed dose-dependent downregulation of p53, Sesn2, and phosphorylated-AMPK with concomitant increase in phosphorylated-p70S6K level than paraquat-treated cells. The differential level of Sesn2 in study subjects proposes its utility as one of the potential serum markers in PD. The ethanolic extract of S aromaticum may serve as a novel platform for management of PD-associated neurotoxicity.

Can People with Parkinson’s Disease Self-Trigger Gait Initiation? A Comparison of Cueing Strategies

2021 ◽  
pp. 1-13
Author(s):  
Matthew N. Petrucci ◽  
Sommer Amundsen Huffmaster ◽  
Jae Woo Chung ◽  
Elizabeth T. Hsiao-Wecksler ◽  
Colum D. MacKinnon
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Young Adults ◽  
Older Adult ◽  
Freezing Of Gait ◽  
External Source ◽  
Anticipatory Postural Adjustments ◽  
Gait Initiation ◽  
Healthy Older Adults

Background: An external cue can markedly improve gait initiation in people with Parkinson’s disease (PD) and is often used to overcome freezing of gait (FOG). It is unknown if the effects of external cueing are comparable if the imperative stimulus is triggered by the person receiving the cue (self-triggered) or an external source. Objective: Two experiments were conducted to compare the effects of self- versus externally triggered cueing on anticipatory postural adjustments (APAs) during gait initiation in people with PD. Methods: In experiment 1, 10 individuals with PD and FOG initiated gait without a cue or in response to a stimulus triggered by the experimenter or by the participant. Experiment 2 compared self- versus externally triggered cueing across three groups: healthy young adults (n = 16), healthy older adults (n = 11), and a group with PD (n = 10). Results: Experiment 1: Externally triggered cues significantly increased APA magnitudes compared to uncued stepping, but not when the same cue was self-triggered. Experiment 2: APAs were not significantly improved with a self-triggered cue compared to un-cued stepping in both the PD and healthy older adult groups, but the young adults showed a significant facilitation of APA magnitude. Conclusion: The effectiveness of an external cue on gait initiation in people with PD and older adults is critically dependent upon whether the source of the trigger is endogenous (self-produced) or exogenous (externally generated). These results may explain why cueing interventions that rely upon self-triggering of the stimulus are often ineffective in people with PD.

scholarly journals Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an In Vitro Model of Parkinson’s Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 326 ◽  
Author(s):  
Nadia Ferlazzo ◽  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Caterina Russo ◽  
Giovanni Enrico Lombardo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nuclear Translocation ◽  
Neuroprotective Effect ◽  
Neuroblastoma Cells ◽  
Specific Cell ◽  
Protective Effects ◽  
Human Neuroblastoma

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H2O2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or H2O2 resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or H2O2. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in cell-free assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.

Gynostemma pentaphyllum Ethanolic Extract Protects Against Memory Deficits in an MPTP-Lesioned Mouse Model of Parkinson's Disease Treated with L-DOPA

2017 ◽  
Vol 20 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Kyung Sook Kim ◽  
Ting Ting Zhao ◽  
Keon Sung Shin ◽  
Hyun Jin Park ◽  
Yoon Jeong Cho ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Ethanolic Extract ◽  
Memory Deficits ◽  
Gynostemma Pentaphyllum

scholarly journals A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity

2017 ◽  
Vol 114 (6) ◽  
pp. E1009-E1017 ◽  
Author(s):  
Michele Perni ◽  
Céline Galvagnion ◽  
Alexander Maltsev ◽  
Georg Meisl ◽  
Martin B. D. Müller ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Natural Product ◽  
Self Assembly ◽  
Lipid Membranes ◽  
Neuroblastoma Cells ◽  
Lipid Vesicles ◽  
Human Neuroblastoma

The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.

scholarly journals Neuroinductive properties of mGDNF depend on the producer, E. Coli or human cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258289
Author(s):  
Dzhirgala V. Shamadykova ◽  
Dmitry Y. Panteleev ◽  
Nadezhda N. Kust ◽  
Ekaterina A. Savchenko ◽  
Ekaterina Y. Rybalkina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ganglion Cells ◽  
Neuroblastoma Cells ◽  
Human Cells ◽  
Hek293 Cells ◽  
Human Neuroblastoma ◽  
Mammalian Expression

The glial cell line‐derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson’s disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson’s disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson’s disease.

scholarly journals A Novel Approach to Treating Anxiety and Enhancing Executive Skills in an Older Adult With Parkinson’s Disease

2009 ◽  
Vol 9 (1) ◽  
pp. 74-90 ◽  
Author(s):  
Jan Mohlman ◽  
Dorian Hunter Reel ◽  
Daniel Chazin ◽  
Diana Ong ◽  
Bianca Georgescu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older Adult ◽  
Novel Approach ◽  
Executive Skills
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