scholarly journals Role of Genes and Treatments for Parkinson’s Disease

2020 ◽  
Vol 8 (1) ◽  
pp. 47-65
Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Treatment Strategies ◽  
Number Of Genes ◽  
Permanent Cure

Parkinson’s Disease (PD) is a complex neurodegenerative disorder that mainly results due to the loss of dopaminergic neurons in the substantia nigra of the midbrain. It is well known that dopamine is synthesized in substantia nigra and is transported to the striatum via nigrostriatal tract. Besides the sporadic forms of PD, there are also familial cases of PD and number of genes (both autosomal dominant as well as recessive) are responsible for PD. There is no permanent cure for PD and to date, L-dopa therapy is considered to be the best option besides having dopamine agonists. In the present review, we have described the genes responsible for PD, the role of dopamine, and treatment strategies adopted for controlling the progression of PD in humans.

Parkinson's Disease

2019 ◽  
pp. 252-273 ◽  
Author(s):  
Vaibhav Walia ◽  
Ashish Gakkhar ◽  
Munish Garg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Older Patients ◽  
Neurodegenerative Disorder ◽  
Progressive Loss ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder in which a progressive loss of the dopaminergic neurons occurs. The loss of the neurons is most prominent in the substantia nigra region of the brain. The prevalence of PD is much greater among the older patients suggesting the risk of PD increases with the increase of age. The exact cause of the neurodegeneration in PD is not known. In this chapter, the authors introduce PD, demonstrate its history, pathogenesis, neurobiology, sign and symptoms, diagnosis, and pharmacotherapy.

scholarly journals Association Between Decreased Srpk3 Expression And An Increase In Substantia Nigra Alpha-Synuclein Levels In An MPTP-Induced Parkinson’s Disease Mouse Model

2022 ◽  
Author(s):  
Min Hyung Seo ◽  
Sujung Yeo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Cell Loss ◽  
Alpha Synuclein ◽  
Mice Model ◽  
Dopaminergic Cell ◽  
The Brain

Abstract Parkinson’s disease (PD) is known as the second most common neurodegenerative disease, which is caused by destruction of dopaminergic neurons in the substantia nigra (SN) of the brain; however, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) is considered an important factor in the pathogenesis of PD. In the current study, we investigated the association between PD and serine/arginine-rich protein specific kinase 3 (Srpk3) in MPTP-induced parkinsonism mice model and in SH-SY5Y cells treated with MPP+. Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) decreased and α-synuclein (α-syn) increased after 4 weeks of MPTP intoxication treatment. Dopaminergic cell reduction and α-syn increase were demonstrated by inhibiting Srpk3 expression by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn increase in SH-SY5Y cells treated with MPP+. These results suggest that the decrease in Srpk3 expression due to Srpk3 siRNA caused both a decrease in TH and an increase in α-syn. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to the pathogenesis of PD. Our results provide an avenue for understanding the role of Srpk3 during dopaminergic cell loss and α-syn increase in the SN. Furthermore, this study could support a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibited dopaminergic cell reduction.

scholarly journals Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Wei Huang ◽  
Qiankun Lv ◽  
Yunfei Xiao ◽  
Zhen Zhong ◽  
Binbin Hu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Human Genetics ◽  
Neurodegenerative Disorder ◽  
Inflammatory Factors ◽  
Inflammatory Mechanism

Parkinson’s disease is a neurodegenerative disorder with an inflammatory response as the core pathogenic mechanism. Previous human genetics findings support the view that the loss of TREM2 function will aggravate neurodegeneration, and TREM2 is one of the most highly expressed receptors in microglia. However, the role of TREM2 in the inflammatory mechanism of PD is not clear. In our study, it was found both in vivo and in vitro that the activation of microglia not only promoted the secretion of inflammatory factors but also decreased the level of TREM2 and inhibited the occurrence of autophagy. In contrast, an increase in the level of TREM2 decreased the expression of inflammatory factors and enhanced the level of autophagy through the p38 MAPK/mTOR pathway. Moreover, increased TREM2 expression significantly decreased the apoptosis of dopaminergic (DA) neurons and improved the motor ability of PD mice. In summary, TREM2 is an important link between the pathogenesis of PD and inflammation. Our study provides a new view for the mechanism of TREM2 in PD and reveals TREM2 as a potential therapeutic target for PD.

scholarly journals Venoms as an adjunctive therapy for Parkinson’s disease: where are we now and where are we going?

2021 ◽  
Vol 7 (2) ◽  
pp. FSO642
Author(s):  
Parisa Gazerani
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Treatment Strategies ◽  
Neuronal Loss ◽  
Diverse Range ◽  
Dopaminergic Neuronal Loss ◽  
New Treatment ◽  
Psychiatric Impairments

Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in the aging population. Crucially, neurodegeneration of dopaminergic neurons in PD is associated with chronic inflammation and glial activation. Besides this, bradykinesia, resting tremor, rigidity, sensory alteration, and cognitive and psychiatric impairments are also present in PD. Currently, no pharmacologically effective treatment alters the progression of the disease. Discovery and development of new treatment strategies remains a focus for ongoing investigations. For example, one approach is cell therapy to prevent dopaminergic neuronal loss or to slow PD progression. The neuroprotective role of a diverse range of natural products, including venoms from bees, scorpions, snakes and lizards, are also being tested in preclinical PD models and in humans. The main findings from recent studies that have investigated venoms as therapeutic options for PD are summarized in this special report.

scholarly journals Forced exercise activates the NrF2 pathway in the striatum and ameliorates motor and behavioral manifestations of Parkinson's disease in rotenone-treated rats

2020 ◽  
Author(s):  
Dina Monir ◽  
Motamed Mahmoud ◽  
Omyma Galal ◽  
Ibrahim Rehan ◽  
Amany Abdelrahman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Short Term Memory ◽  
Treadmill Exercise ◽  
Neurodegenerative Disorder ◽  
Short Term ◽  
Term Memory ◽  
Nrf2 Pathway

Abstract Background: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons leading to dopamine depletion and problems of movement, emotions and cognition. While the pathogenesis of PD is not clear, damage of dopaminergic neurons by oxygen-derived free radicals is considered an important contributing mechanism.This study aimed to evaluate the role of treadmill exercise in male Wister rats as a single treatment and as an aid-therapy with L-dopa for rotenone-induced PD. To study the role of NRF2-ARE pathway as a mechanism involved in exercise associated improvement in rotenone rat model of PD.Method: Animals were divided into 5 groups, (Control, rotenone, rotenone\exercise, rotenone\L-dopa, and rotenone\exercise\L-dopa (combination) groups). After the PD induction, rats in the rotenone\exercise and combination groups were daily treadmill exercised for 4 weeks.Results: Treadmill exercise significantly improved behavioral and motor aspects of rotenone model of PD. When treadmill exercise introduced as a single intervention, it amended most behavioral aspects of PD, gait fully corrected, short-term memory, and motor coordination. Where L-dopa corrected locomotor activity and motor co-ordination but failed to improve short-term memory and only partially corrected the gait of rotenone-treated rats. When treadmill exercise was combined with L-dopa, all features of PD were corrected. It was found that exercise upregulated some of its associative genes to NRF2 pathways such as TFAM, NRF2, Noq.1 mRNA expression.Conclusion: This study suggests that forced exercise improved parkinsonian like features by activating NRF2 pathway.

scholarly journals Treating Parkinson’s disease by astrocyte reprogramming: Progress and challenges

2021 ◽  
Vol 7 (26) ◽  
pp. eabg3198
Author(s):  
Zhuang-Yao D. Wei ◽  
Ashok K. Shetty
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Nonmotor Symptoms ◽  
Axonal Projections ◽  
Potential Risks

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is typified by both motor and nonmotor symptoms. The current medications provide symptomatic relief but do not stimulate the production of new dopaminergic neurons in the substantia nigra. Astrocyte reprogramming has recently received much attention as an avenue for increasing functional dopaminergic neurons in the mouse PD brain. By targeting a microRNA (miRNA) loop, astrocytes in the mouse brain could be reprogrammed into functional dopaminergic neurons. Such in vivo astrocyte reprogramming in the mouse model of PD has successfully added new dopaminergic neurons to the substantia nigra and increased dopamine levels associated with axonal projections into the striatum. This review deliberates the astrocyte reprogramming methods using specific transcription factors and mRNAs and the progress in generating dopaminergic neurons in vivo. In addition, the translational potential, challenges, and potential risks of astrocyte reprogramming for an enduring alleviation of parkinsonian symptoms are conferred.

scholarly journals Neurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8421
Author(s):  
Chrysoula Marogianni ◽  
Maria Sokratous ◽  
Efthimios Dardiotis ◽  
Georgios M. Hadjigeorgiou ◽  
Dimitrios Bogdanos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Viral Infections ◽  
Neurodegenerative Disorder ◽  
Epidemiological Studies ◽  
In Vitro Models ◽  
Immune Mediated

Parkinson’s disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut–brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.

scholarly journals Methamphetamine and Parkinson's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Noelia Granado ◽  
Sara Ares-Santos ◽  
Rosario Moratalla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Motor Impairment ◽  
Gene Mutations ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Significant Loss

Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles.

scholarly journals Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

2018 ◽  
Vol 19 (10) ◽  
pp. 2973 ◽  
Author(s):  
Anastasiia Bohush ◽  
Grazyna Niewiadomska ◽  
Anna Filipek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Map Kinases ◽  
Clinical Symptoms ◽  
Neurodegenerative Disorder ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Important Player

Parkinson’s disease (PD) is a neurodegenerative disorder caused by insufficient dopamine production due to the loss of 50% to 70% of dopaminergic neurons. A shortage of dopamine, which is predominantly produced by the dopaminergic neurons within the substantia nigra, causes clinical symptoms such as reduction of muscle mass, impaired body balance, akinesia, bradykinesia, tremors, postural instability, etc. Lastly, this can lead to a total loss of physical movement and death. Since no cure for PD has been developed up to now, researchers using cell cultures and animal models focus their work on searching for potential therapeutic targets in order to develop effective treatments. In recent years, genetic studies have prominently advocated for the role of improper protein phosphorylation caused by a dysfunction in kinases and/or phosphatases as an important player in progression and pathogenesis of PD. Thus, in this review, we focus on the role of selected MAP kinases such as JNKs, ERK1/2, and p38 MAP kinases in PD pathology.

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