scholarly journals Peripheral Delivery of Neural Precursor Cells Ameliorates Parkinson’s Disease-Associated Pathology

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1359 ◽  
Author(s):  
Edwards III ◽  
Gamez ◽  
Armijo ◽  
Kramm ◽  
Morales ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Motor Function ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Clinical Signs ◽  
Alpha Synuclein ◽  
Neuroinflammatory Response ◽  
Impaired Motor Function

: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by loss of motor control due to a wide loss of dopaminergic neurons along the nigro-striatal pathway. Some of the mechanisms that contribute to this cell death are inflammation, oxidative stress, and misfolded alpha-synuclein-induced toxicity. Current treatments are effective at managing the early motor symptoms of the disease, but they become ineffective over time and lead to adverse effects. Previous research using intracerebral stem cell therapy for treatment of PD has provided promising results; however, this method is very invasive and is often associated with unacceptable side effects. In this study, we used an MPTP-injected mouse model of PD and intravenously administered neural precursors (NPs) obtained from mouse embryonic and mesenchymal stem cells. Clinical signs and neuropathology were assessed. Female mice treated with NPs had improved motor function and reduction in the neuroinflammatory response. In terms of safety, there were no tumorigenic formations or any detectable adverse effect after treatment. Our results suggest that peripheral administration of stem cell-derived NPs may be a promising and safe therapy for the recovery of impaired motor function and amelioration of brain pathology in PD.

scholarly journals Nicotinamide mononucleotide treatment increases NAD+ levels in an iPSC Model of Parkinson’s Disease but does not impact sirtuin activity

2020 ◽  
Author(s):  
Brett Fulleylove-Krause ◽  
Samantha Sison ◽  
Allison Ebert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Nicotinamide Mononucleotide ◽  
Reduce Activity ◽  
Underlying Mechanisms ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Dopaminergic Neuron Loss

Abstract Objectives: Parkinson’s disease (PD) is a common neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although the underlying mechanisms of dopaminergic neuron loss is not fully understood, evidence suggests mitochondrial malfunction as a key contributor to disease pathogenesis. We previously found that human PD patient stem cell-derived dopaminergic neurons exhibit reduced nicotinamide adenine dinucleotide (NAD+) levels and reduce activity of sirtuins, a group of NAD+-dependent deacetylase enzymes that participate in the regulation of mitochondrial function, energy production, and cell survival. Thus, here we tested whether treatment of PD stem cell-derived dopaminergic neurons with nicotinamide mononucleotide (NMN), an NAD+ precursor, could increase NAD+ levels and improve sirtuin activity. Results: We treated PD iPSC-derived dopaminergic neurons with NMN and found that NAD+ levels did increase. The deacetylase activity of sirtuin (SIRT) 2 was improved with NMN treatment, but NMN had no impact on deacetylase activity of SIRT 1 or 3. These results suggest that NMN can restore NAD+ levels and SIRT 2 activity, but that additional mechanisms are involved SIRT 1 and 3 dysregulation in PD dopaminergic neurons.

Effect of Cabergoline on Cognitive Impairments in Transgenic Drosophila Model of Parkinson’s Disease

2020 ◽  
Vol 17 (10) ◽  
pp. 1261-1269
Author(s):  
Yasir Hasan Siddique ◽  
Rahul ◽  
Mantasha Idrisi ◽  
Mohd. Shahid
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Cognitive Impairments ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Positive Interaction ◽  
Drosophila Model ◽  
Transgenic Drosophila

Background: Parkinson’s disease is a common neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Introduction: The effects of alpha synuclein, parkin mutation and pharmacological agents have been studied in the Drosophila model. Methods: The effect of cabergoline was studied on the cognitive impairments exhibited by the transgenic Drosophila expressing human alpha-synuclein in the neurons. The PD flies were allowed to feed on the diet having 0.5, 1 and 1.5 μM of cabergoline. Results and Discussion: The exposure of cabergoline not only showed a dose-dependent significant delay in the cognitive impairments but also prevented the loss of dopaminergic neurons. Molecular docking studies showed the positive interaction between cabergoline and alpha-synuclein. Conclusion: The results suggest a protective effect of cabergoline against the cognitive impairments.

scholarly journals Nicotinamide mononucleotide treatment increases NAD+ levels in an iPSC Model of Parkinson’s Disease

2020 ◽  
Author(s):  
Brett K. Fulleylove-Krause ◽  
Samantha L. Sison ◽  
Allison D. Ebert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Mitochondrial Function ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Motor Deficits ◽  
Severe Motor ◽  
Underlying Mechanisms ◽  
Reduced Nicotinamide Adenine Dinucleotide

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra that leads to severe motor and non-motor deficits. Although the underlying mechanisms of dopaminergic neuron loss is not entirely clear, increasing evidence suggests mitochondrial malfunction as a key contributor to disease pathogenesis. Recently, we found that human PD patient stem cell-derived dopaminergic neurons exhibit reduced nicotinamide adenine dinucleotide (NAD+) levels, an essential cofactor in mitochondrial function and cellular metabolism. In addition, we found that sirtuins, a group of NAD+-dependent deacetylase enzymes that participate in the regulation of mitochondrial function, energy production, and cell survival, displayed decreased activity in PD dopaminergic neurons, thereby suggesting a potential mechanism for dopaminergic loss in PD. Thus, here we tested whether treatment of PD stem cell-derived dopaminergic neurons with an NAD+ precursor could increase NAD+ levels and improve sirtuin activity.

scholarly journals Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2182 ◽  
Author(s):  
Richard L. Jayaraj ◽  
Rami Beiram ◽  
Sheikh Azimullah ◽  
Mohamed Fizur Nagoor Meeran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Stress Factors ◽  
Definitive Treatment ◽  
And Oxidative Stress

Parkinson’s disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug’s multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD.

scholarly journals Alpha-Synuclein Aggregation in Parkinson's Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
E. Srinivasan ◽  
G. Chandrasekhar ◽  
P. Chandrasekar ◽  
K. Anbarasu ◽  
A. S. Vickram ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Alpha Synuclein ◽  
Substantia Nigra Pars Compacta ◽  
Vulnerability Factors ◽  
Alpha Synuclein Aggregation

Parkinson's disease (PD), a neurodegenerative disorder characterized by distinct aging-independent loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region urging toward neuronal loss. Over the decade, various key findings from clinical perspective to molecular pathogenesis have aided in understanding the genetics with assorted genes related with PD. Subsequently, several pathways have been incriminated in the pathogenesis of PD, involving mitochondrial dysfunction, protein aggregation, and misfolding. On the other hand, the sporadic form of PD cases is found with no genetic linkage, which still remain an unanswered question? The exertion in ascertaining vulnerability factors in PD considering the genetic factors are to be further dissevered in the forthcoming decades with advancement in research studies. One of the major proponents behind the prognosis of PD is the pathogenic transmutation of aberrant alpha-synuclein protein into amyloid fibrillar structures, which actuates neurodegeneration. Alpha-synuclein, transcribed by SNCA gene is a neuroprotein found predominantly in brain. It is implicated in the modulation of synaptic vesicle transport and eventual release of neurotransmitters. Due to genetic mutations and other elusive factors, the alpha-synuclein misfolds into its amyloid form. Therefore, this review aims in briefing the molecular understanding of the alpha-synuclein associated with PD.

scholarly journals Novel Immunotherapeutic Approaches to Target Alpha-Synuclein and Related Neuroinflammation in Parkinson’s Disease

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 105 ◽  
Author(s):  
Maria Zella ◽  
Judith Metzdorf ◽  
Friederike Ostendorf ◽  
Fabian Maass ◽  
Siegfried Muhlack ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Glial Cell ◽  
Dopaminergic Neurons ◽  
Basic Research ◽  
Alpha Synuclein ◽  
Models Of Disease ◽  
Novel Therapeutic Strategies ◽  
Lymphocyte Populations

The etiology of Parkinson’s disease (PD) is significantly influenced by disease-causing changes in the protein alpha-Synuclein (aSyn). It can trigger and promote intracellular stress and thereby impair the function of dopaminergic neurons. However, these damage mechanisms do not only extend to neuronal cells, but also affect most glial cell populations, such as astroglia and microglia, but also T lymphocytes, which can no longer maintain the homeostatic CNS milieu because they produce neuroinflammatory responses to aSyn pathology. Through precise neuropathological examination, molecular characterization of biomaterials, and the use of PET technology, it has been clearly demonstrated that neuroinflammation is involved in human PD. In this review, we provide an in-depth overview of the pathomechanisms that aSyn elicits in models of disease and focus on the affected glial cell and lymphocyte populations and their interaction with pathogenic aSyn species. The interplay between aSyn and glial cells is analyzed both in the basic research setting and in the context of human neuropathology. Ultimately, a strong rationale builds up to therapeutically reduce the burden of pathological aSyn in the CNS. The current antibody-based approaches to lower the amount of aSyn and thereby alleviate neuroinflammatory responses is finally discussed as novel therapeutic strategies for PD.

scholarly journals Stem Cell Therapy: A Promising Treatment of Parkinson’s Diseases

2021 ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Dopaminergic Neurons ◽  
Cellular Therapy ◽  
Neurodegenerative Disorder ◽  
Neuronal Degeneration ◽  
Cell Types ◽  
Parkinson’S Diseases ◽  
Multipotent Mesenchymal Stem Cells

The neurodegenerative disorder is a prolonged persistence curse and effect on economic and physical challenges in an aging world. Parkinson has come in the second category of disability disorders and associated with progressive dopaminergic neuronal degeneration with severe motor complications. It is an observation that gradual disease progression causes 70% degeneration of striatal dopaminergic neurons. Globally there are around 7-10 million patients with Parkinson's disease, however, there are huge efforts for therapeutic improvement. According to studies, no single molecular pathway was pointed out as a single etiology to control disease progression due to a lack of targeted therapeutic strategies. Previously implemented symptomatic treatments include L-dopa (L-3,4-dihydroxyphenylalanine), deep brain stimulation, and the surgical insertion of a medical device. This leads to dyskinesia, dystonia and a higher risk of major surgical complications respectively. However, not all the above-mentioned therapies cannot regenerate the dopaminergic neurons in Parkinson’s disease patients. Recent advances in the field of cellular therapy have shown promising outcomes by differentiation of multipotent mesenchymal stem cells into dopaminergic neurons under the influence of a regenerative substance. In this review, we have discussed the differentiation of dopaminergic neurons by using different cell types that can be used as a cellular therapeutic approach for Parkinson’s disease. The information was collected through a comprehensive search using the keywords, “Parkinson Disease, Dopamine, Brain derived neurotrophic factor and neuron from reliable search engines, PubMed, Google Scholar and Medline reviews from the year 2010 to 2020.

scholarly journals Alpha-Synuclein Induced Immune Cells Activation and Associated Therapy in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Ruichen Su ◽  
Tian Zhou
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Immune Cells ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Autoimmune Response ◽  
T Helper ◽  
Helper Type

Parkinson’s disease (PD) is a neurodegenerative disorder closely related to immunity. An important aspect of the pathogenesis of PD is the interaction between α-synuclein and a series of immune cells. Studies have shown that accumulation of α-synuclein can induce an autoimmune response that accelerates the progression of PD. This study discusses the mechanisms underlying the interaction between α-synuclein and the immune system. During the development of PD, abnormally accumulated α-synuclein becomes an autoimmune antigen that binds to Toll-like receptors (TLRs) that activate microglia, which differentiate into the microglia type 1 (M1) subtype. The microglia activate intracellular inflammatory pathways, induce the release of proinflammatory cytokines, and promote the differentiation of cluster of differentiation 4 + (CD4 +) T cells into proinflammatory T helper type 1 (Th1) and T helper type 17 (Th17) subtypes. Given the important role of α-synuclein in the immune system of the patients with PD, identifying potential targets of immunotherapy related to α-synuclein is critical for slowing disease progression. An enhanced understanding of immune-associated mechanisms in PD can guide the development of associated therapeutic strategies in the future.

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.

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