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.

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 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.

scholarly journals Modelling Parkinson’s Disease: iPSCs towards Better Understanding of Human Pathology

2021 ◽  
Vol 11 (3) ◽  
pp. 373
Author(s):  
Sahar Avazzadeh ◽  
Jara Maria Baena ◽  
Cameron Keighron ◽  
Yajaira Feller-Sanchez ◽  
Leo R. Quinlan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Gene Mutations ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Human Pathology ◽  
Different Genetic Background ◽  
Cellular Phenotypes

Parkinson’s Disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms, among which are bradykinesia, rigidity, tremor as well as mental symptoms such as dementia. The underlying cause of Parkinson disease is degeneration of dopaminergic neurons. It has been challenging to develop an efficient animal model to accurately represent the complex phenotypes found with PD. However, it has become possible to recapitulate the myriad of phenotypes underlying the PD pathology by using human induced pluripotent stem cell (iPSC) technology. Patient-specific iPSC-derived dopaminergic neurons are available and present an opportunity to study many aspects of the PD phenotypes in a dish. In this review, we report the available data on iPSC-derived neurons derived from PD patients with identified gene mutations. Specifically, we will report on the key phenotypes of the generated iPSC-derived neurons from PD patients with different genetic background. Furthermore, we discuss the relationship these cellular phenotypes have to PD pathology and future challenges and prospects for iPSC modelling and understanding of the pathogenesis of PD.

scholarly journals The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Khairiah Razali ◽  
Noratikah Othman ◽  
Mohd Hamzah Mohd Nasir ◽  
Abd Almonem Doolaanea ◽  
Jaya Kumar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Large Scale ◽  
Neurodegenerative Disorder ◽  
Model Organism ◽  
The Elderly ◽  
Zebrafish Model ◽  
Mao B ◽  
Viable Model

The second most prevalent neurodegenerative disorder in the elderly is Parkinson’s disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.

scholarly journals Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

2021 ◽  
Vol 13 ◽  
Author(s):  
Upasana Ganguly ◽  
Sukhpal Singh ◽  
Soumya Pal ◽  
Suvarna Prasad ◽  
Bimal K. Agrawal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorders ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Motor Impairment ◽  
The Elderly ◽  
Alpha Synuclein ◽  
Cross Sectional ◽  
Peripheral Tissues

Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

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 GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease

2020 ◽  
Author(s):  
Urmila Maitra ◽  
Thomas Harding ◽  
Qiaoli Liang ◽  
Lukasz Ciesla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Epidemiological Studies ◽  
Ultra Performance Liquid Chromatography ◽  
Drosophila Model ◽  
Environmental Toxin

AbstractParkinson’s disease (PD) is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide, paraquat (PQ) as major contributors to PD etiology in both mammalian and invertebrate models. We have employed a PQ-induced PD model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against PQ-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully detected GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced PD pathogenesis for novel therapeutic intervention.

scholarly journals Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

2020 ◽  
Vol 14 ◽  
Author(s):  
Xiangpeng Ren ◽  
Jiang-Fan Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Studies ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Motor Impairment ◽  
Epidemiological Studies ◽  
Experimental Investigations ◽  
Caffeine Consumption ◽  
Dopaminergic Neurodegeneration

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neurodegeneration, motor impairment and non-motor symptoms. Epidemiological and experimental investigations into potential risk factors have firmly established that dietary factor caffeine, the most-widely consumed psychoactive substance, may exerts not only neuroprotective but a motor and non-motor (cognitive) benefits in PD. These multi-benefits of caffeine in PD are supported by convergence of epidemiological and animal evidence. At least six large prospective epidemiological studies have firmly established a relationship between increased caffeine consumption and decreased risk of developing PD. In addition, animal studies have also demonstrated that caffeine confers neuroprotection against dopaminergic neurodegeneration using PD models of mitochondrial toxins (MPTP, 6-OHDA, and rotenone) and expression of α-synuclein (α-Syn). While caffeine has complex pharmacological profiles, studies with genetic knockout mice have clearly revealed that caffeine’s action is largely mediated by the brain adenosine A2A receptor (A2AR) and confer neuroprotection by modulating neuroinflammation and excitotoxicity and mitochondrial function. Interestingly, recent studies have highlighted emerging new mechanisms including caffeine modulation of α-Syn degradation with enhanced autophagy and caffeine modulation of gut microbiota and gut-brain axis in PD models. Importantly, since the first clinical trial in 2003, United States FDA has finally approved clinical use of the A2AR antagonist istradefylline for the treatment of PD with OFF-time in Sept. 2019. To realize therapeutic potential of caffeine in PD, genetic study of caffeine and risk genes in human population may identify useful pharmacogenetic markers for predicting individual responses to caffeine in PD clinical trials and thus offer a unique opportunity for “personalized medicine” in PD.

scholarly journals GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Urmila Maitra ◽  
Thomas Harding ◽  
Qiaoli Liang ◽  
Lukasz Ciesla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Disease Model ◽  
Epidemiological Studies ◽  
Disease Etiology ◽  
Environmental Toxin

AbstractParkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide paraquat as major contributors to Parkinson’s disease etiology in both mammalian and invertebrate models. We have employed a paraquat-induced Parkinson’s disease model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against paraquat-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully shown GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced Parkinson’s disease pathogenesis for novel therapeutic intervention.

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.

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