scholarly journals Dual target strategy: combining distinct non-dopaminergic treatments reduces neuronal cell loss and synergistically modulates l -DOPA-induced rotational behavior in a rodent model of Parkinson's disease

2015 ◽  
Vol 134 (4) ◽  
pp. 740-747 ◽  
Author(s):  
Marie-Therese Fuzzati-Armentero ◽  
Silvia Cerri ◽  
Giovanna Levandis ◽  
Giulia Ambrosi ◽  
Elena Montepeloso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Rodent Model ◽  
Rotational Behavior ◽  
Neuronal Cell Loss ◽  
Target Strategy ◽  
Dual Target

A Nucleoprotein-Enriched Diet Suppresses Dopaminergic Neuronal Cell Loss and Motor Deficit in Mice with MPTP-Induced Parkinson’s Disease

2014 ◽  
Vol 55 (3) ◽  
pp. 803-811 ◽  
Author(s):  
Keisuke Kiriyama ◽  
Hirokazu Ohtaki ◽  
Natsuki Kobayashi ◽  
Norimitsu Murai ◽  
Minako Matsumoto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Motor Deficit ◽  
Dopaminergic Neuronal Cell ◽  
Neuronal Cell Loss

A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson’s disease

2020 ◽  
Vol 12 (560) ◽  
pp. eaau3960
Author(s):  
Ibrahim Boussaad ◽  
Carolin D. Obermaier ◽  
Zoé Hanss ◽  
Dheeraj R. Bobbili ◽  
Silvia Bolognin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Neuronal Cell ◽  
Exon Skipping ◽  
Cell Loss ◽  
Genetically Engineered ◽  
Neuronal Precursor Cells

Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of PARK7-linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial dysfunction. Targeting defective exon skipping with genetically engineered U1-snRNA recovered DJ-1 protein expression in neuronal precursor cells and differentiated neurons. After prioritization of candidate drugs, we identified and validated a combinatorial treatment with the small-molecule compounds rectifier of aberrant splicing (RECTAS) and phenylbutyric acid, which restored DJ-1 protein and mitochondrial dysfunction in patient-derived fibroblasts as well as dopaminergic neuronal cell loss in mutant midbrain organoids. Our analysis of a large number of exomes revealed that U1 splice-site mutations were enriched in sporadic PD patients. Therefore, our study suggests an alternative strategy to restore cellular abnormalities in in vitro models of PD and provides a proof of concept for neuroprotection based on precision medicine strategies in PD.

scholarly journals PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3329
Author(s):  
Yeon Joo Choi ◽  
Dae Won Kim ◽  
Min Jea Shin ◽  
Hyeon Ji Yeo ◽  
Eun Ji Yeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Dopaminergic Neurons ◽  
Therapeutic Agent ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Dopaminergic Neuronal Cell ◽  
Apoptosis Related Protein

Parkinson’s disease (PD) is characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SN) mediated via oxidative stress. Although glutaredoxin-1 (GLRX1) is known as one of the antioxidants involved in cell survival, the effects of GLRX1 on PD are still unclear. In this study, we investigated whether cell-permeable PEP-1-GLRX1 inhibits dopaminergic neuronal cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We showed that PEP-1-GLRX1 protects cell death and DNA damage in MPP+-exposed SH-SY5Y cells via the inhibition of MAPK, Akt, and NF-κB activation and the regulation of apoptosis-related protein expression. Furthermore, we found that PEP-1-GLRX1 was delivered to the SN via the blood–brain barrier (BBB) and reduced the loss of dopaminergic neurons in the MPTP-induced PD model. These results indicate that PEP-1-GLRX1 markedly inhibited the loss of dopaminergic neurons in MPP+- and MPTP-induced cytotoxicity, suggesting that this fusion protein may represent a novel therapeutic agent against PD.

scholarly journals Pyrethroid exposure and neurotoxicity: a mechanistic approach

2019 ◽  
Vol 70 (2) ◽  
pp. 74-89 ◽  
Author(s):  
Hamidreza Mohammadi ◽  
Nasrin Ghassemi-Barghi ◽  
Obeid Malakshah ◽  
Sorour Ashari
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurological Disorders ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Future Research ◽  
Dopaminergic Neurodegeneration ◽  
Mechanistic Approach ◽  
Disease Therapy ◽  
Nigrostriatal Dopaminergic Neurodegeneration

AbstractPyrethroids are a class of synthetic insecticides that are used widely in and around households to control the pest. Concerns about exposure to this group of pesticides are now mainly related to their neurotoxicity and nigrostriatal dopaminergic neurodegeneration seen in Parkinson’s disease. The main neurotoxic mechanisms include oxidative stress, inflammation, neuronal cell loss, and mitochondrial dysfunction. The main neurodegeneration targets are ion channels. However, other receptors, enzymes, and several signalling pathways can also participate in disorders induced by pyrethroids. The aim of this review is to elucidate the main mechanisms involved in neurotoxicity caused by pyrethroids deltamethrin, permethrin, and cypermethrin. We also review common targets and pathways of Parkinson’s disease therapy, including Nrf2, Nurr1, and PPARγ, and how they are affected by exposure to pyrethroids. We conclude with possibilities to be addressed by future research of novel methods of protection against neurological disorders caused by pesticides that may also find their use in the management/treatment of Parkinson’s disease.

scholarly journals Alpha-Synuclein in Parkinson’s Disease: From Pathogenetic Dysfunction to Potential Clinical Application

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lingjia Xu ◽  
Jiali Pu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Current Knowledge ◽  
Point Mutations ◽  
Lewy Bodies ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Lewy Neurites

Parkinson’s disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of theα-synuclein protein (encoded by theSNCAgene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson’s disease. TheSNCAgene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism ofα-synuclein in Parkinson’s disease remains obscure. Recent research showed that variousα-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson’s disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction ofα-synuclein associated with Parkinson’s disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target.

scholarly journals Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 612
Author(s):  
Frank C. Church
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Management Program ◽  
Additional Treatment ◽  
Substantia Nigra Pars Compacta ◽  
Speech Pathology

Parkinson’s disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson’s (PwP): rehabilitate, therapy, restorative, maintenance, and surgery. Rehabilitating begins following the diagnosis and throughout any additional treatment processes, especially vis-à-vis consulting with physical, occupational, and/or speech pathology therapist(s). Therapy uses daily administration of either the dopamine precursor levodopa (with carbidopa) or a dopamine agonist, compounds that preserve residual dopamine, and other specific motor/non-motor-related compounds. Restorative uses strenuous aerobic exercise programs that can be neuroprotective. Maintenance uses complementary and alternative medicine substances that potentially support and protect the brain microenvironment. Finally, surgery, including deep brain stimulation, is pursued when PwP fail to respond positively to other treatment options. There is currently no cure for PD. In conclusion, the best strategy for treating PD is to hope to slow disorder progression and strive to achieve stability with neuroprotection. The ultimate goal of any management program is to improve the quality-of-life for a person with Parkinson’s disease.

Effect of Human Umblical Cord Blood Stem Cells on a Rodent Model of Parkinson's Disease

2018 ◽  
Vol 46 (2) ◽  
pp. 117-127
Author(s):  
Somia Abd-Allah ◽  
El-Sayed Abdel-Aziz ◽  
Sabry Ali ◽  
Gamal El-Din Shams ◽  
Hesham Mohammed ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Cord Blood ◽  
Rodent Model ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells

A PPAR-β/δ Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease

2014 ◽  
Vol 11 (2) ◽  
pp. 114-124 ◽  
Author(s):  
Nihar Das ◽  
Rahul Gangwal ◽  
Mangesh Damre ◽  
Abhay Sangamwar ◽  
Shyam Sharma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Rodent Model
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