scholarly journals Stem cells delay disease onset in mice with neurodegenerative disease

2009 ◽  
Author(s):  
Monya Baker
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Disease ◽  
Disease Onset ◽  
Delay Disease Onset

scholarly journals Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Glial Cells ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

Neurodegenerative disease-specific induced pluripotent Stem cells research

2009 ◽  
Vol 65 ◽  
pp. S10
Author(s):  
Haruhisa Inoue ◽  
Shiho Kitaoka ◽  
Motoko Naitoh ◽  
Kazutoshi Takahashi ◽  
Katsuhiro Yoshikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent ◽  
Disease Specific

scholarly journals Therapeutic Potential of Repeated Intravenous Transplantation of Human Adipose-Derived Stem Cells in Subchronic MPTP-Induced Parkinson’s Disease Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8129
Author(s):  
Hyunjun Park ◽  
Keun-A Chang
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Neurodegenerative Disease ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Therapeutic Potential ◽  
Adipose Derived Stem Cells ◽  
Nigrostriatal Pathway

Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.

scholarly journals Enhanced neuronal Met signalling levels in ALS mice delay disease onset

2011 ◽  
Vol 2 (3) ◽  
pp. e130-e130 ◽  
Author(s):  
M Genestine ◽  
E Caricati ◽  
A Fico ◽  
S Richelme ◽  
H Hassani ◽  
...  
Keyword(s):  
Disease Onset ◽  
Delay Disease Onset

scholarly journals Alterations in leptin signaling in Amyotrophic Lateral Sclerosis (ALS)

2021 ◽  
Author(s):  
Agueda Ferrer-Donato ◽  
Ana Contreras ◽  
Laura M. Frago ◽  
Julie A. Chowen ◽  
Carmen M. Fernandez-Martos
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Time Course ◽  
Leptin Receptor ◽  
Expression Profiles ◽  
Disease Onset ◽  
Plasminogen Activator Inhibitor ◽  
Inhibitory Peptide ◽  
Leptin Signaling ◽  
Lateral Sclerosis

Leptin has been suggested to play a role in amyotrophic lateral sclerosis (ALS), a fatal progressive and neurodegenerative disease. This adipokine has previously been shown to be associated with a lower risk of ALS disease and to confer a survival advantage in ALS patients. However, the role of leptin in the progression of ALS is unknown. Indeed, our understanding of the mechanisms underlying leptins effects in the pathogenesis of ALS is very limited, and it is fundamental to determine whether alterations in leptins actions take place in this neurodegenerative disease. To characterize the association between leptin signaling and the clinical course of ALS we assessed the mRNA and protein expression profiles of leptin, the long leptin receptor (Ob-Rb) and leptin-related signaling pathways over the time course of the disease (onset and end-stage of disease), in TDP-43A315T mice compared to age-matched WT littermates. In addition, at the selected time-points immunoassay analysis was conducted to characterize plasma levels of total ghrelin, the adipokines (resistin and leptin) and metabolic proteins (plasminogen activator inhibitor type 1 (PAI-1), gastric inhibitory peptide (GIP), glucagon like peptide 1 (GLP-1), insulin and glucagon) in TDP-43A315T mice compared to WT controls. Our results indicate alterations in leptin signaling in the spinal cord and the hypothalamus on the backdrop of TDP-43-induced deficits in mice, providing new evidence about the pathways that could link leptin signaling to ALS.

scholarly journals Modeling Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex with Microglia Containing Cerebral Organoids Derived from Induced Pluripotent Stem Cells

2021 ◽  
Author(s):  
Yiling Hong ◽  
Xu Dong ◽  
Lawrence Chang ◽  
Mariann Chang ◽  
Chen Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
M2 Microglia ◽  
Matrix Organization ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism dementia Complex (ALS-PDC) is a neurodegenerative disease linked to the traditional consumption of cycad seeds by the Chamorro people of Guam. Little is known about the etiological role of cycad toxin in ALS-PDC. Patient derived induced pluripotent stem cells were derived from age and sex matched affected and unaffected patient lymphoid cells then differentiated into cerebral organoids. After three months, the ALS-PDC affected organoids were smaller, their neurons had less extensive neurite outgrowth, and the organoids had more reactive astrocytes and M1 microglia, fewer resting and M2 microglia, and more open extracellular space. Most of these phenomena could be recapitulated by exposing unaffected organoids to β-methylamino L-alanine (BMAA), a toxic amino acid produced by cyanobacteria living with cycad plants. Furthermore, ALS-PDC affected organoids exhibited an exacerbated neuroinflammatory response to BMAA exposure via activation of caspase1/NLRP3 inflammasome. A genome-wide transcriptome analysis of the organoids showed that the most down regulated pathways were taurine, alanine, aspartate, and glutamate metabolism; protein digestion; and absorption. The most down-regulated biological processes were type I interferon signaling, regulation of neuron differentiation and extracellular matrix organization. Our results suggested that the etiology of ALS-PDC is due to metabolic disorders that shifted microglia to a more proinflammatory M1 state instead of a non-inflammatory, repairing M2 state, which exacerbated inflammation and reduced extracellular matrix strength. Supplementation of transforming growth factor beta to ALS/PDC affected organoids increased the expression of interferon-induced transmembrane proteins (IFITMs) and restored M2 microglia populations and extracellular matrix organization. Organoids containing networks of neurons, astrocytes, microglia derived from iPSC with our protocol provides an excellent cellular model for neurodegenerative disease modeling.

scholarly journals Alterations in Leptin Signaling in Amyotrophic Lateral Sclerosis (ALS)

2021 ◽  
Vol 22 (19) ◽  
pp. 10305
Author(s):  
Agueda Ferrer-Donato ◽  
Ana Contreras ◽  
Laura M. Frago ◽  
Julie A. Chowen ◽  
Carmen M. Fernandez-Martos
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Disease ◽  
Leptin Receptor ◽  
Expression Profiles ◽  
Disease Onset ◽  
Plasminogen Activator Inhibitor ◽  
Inhibitory Peptide ◽  
Leptin Signaling ◽  
Activator Inhibitor Type ◽  
Lateral Sclerosis

Leptin has been suggested to play a role in amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disease. This adipokine has previously been shown to be associated with a lower risk of ALS and to confer a survival advantage in ALS patients. However, the role of leptin in the progression of ALS is unknown. Indeed, our understanding of the mechanisms underlying leptin’s effects in the pathogenesis of ALS is very limited, and it is fundamental to determine whether alterations in leptin’s actions take place in this neurodegenerative disease. To characterize the association between leptin signaling and the clinical course of ALS, we assessed the mRNA and protein expression profiles of leptin, the long-form of the leptin receptor (Ob-Rb), and leptin-related signaling pathways at two different stages of the disease (onset and end-stage) in TDP-43A315T mice compared to age-matched WT littermates. In addition, at selected time-points, an immunoassay analysis was conducted to characterize plasma levels of total ghrelin, the adipokines resistin and leptin, and metabolic proteins (plasminogen activator inhibitor type 1 (PAI-1), gastric inhibitory peptide (GIP), glucagon-like peptide 1 (GLP-1), insulin and glucagon) in TDP-43A315T mice compared to WT controls. Our results indicate alterations in leptin signaling in the spinal cord and the hypothalamus on the backdrop of TDP-43-induced deficits in mice, providing new evidence about the pathways that could link leptin signaling to ALS.

scholarly journals Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes

2021 ◽  
Author(s):  
Jorge Postigo Fernandez ◽  
Remi J Creusot
Keyword(s):  
Precision Medicine ◽  
Specific Immunotherapy ◽  
Dna Vaccines ◽  
Disease Onset ◽  
Delay Disease Onset ◽  
Intradermal Delivery ◽  
Dosing Frequency ◽  
Progression Of Disease

Antigen-specific immunotherapy involves the delivery of self-antigens as proteins or peptides (or using nucleic acids encoding them) to be presented with the goal of inducing tolerance. Approaches employing specific epitopes restricted to the subject's MHC haplotypes have multiplied and offer a more focused and tailored way of targeting autoreactive T cells. In addition, the Endotope platform allows endogenously expressed epitopes to be processed and presented on appropriate MHC class I and II molecules. Here, we evaluated the efficacy of a DNA vaccine encoding epitopes selected and tailored for the non-obese diabetic (NOD) mouse compared to the expression of the proinsulin protein, one of the most successful antigens in prevention of NOD disease, and we assessed the influence of several parameters (e.g. route, dosing frequency) on preventing diabetes onset at normoglycemic and dysglycemic stages. First, encoded peptides should be secreted for effective disease prevention. Furthermore, short weekly treatments with Endotope and proinsulin DNA vaccines delay disease onset, but sustained treatments are required for long-term protection, which was more significant with intradermal delivery. Although epitopes can be presented for at least two weeks, reducing the frequency of antigen administration from weekly to every other week reduced efficacy. Finally, both Endotope and proinsulin DNA vaccines were effective in the dysglycemic stage of disease, but proinsulin provided better protection, particularly in subjects with slower progression of disease. Thus, our data support the possibility of applying a precision medicine approach based on tailored epitopes for the treatment of tissue-specific autoimmune diseases with DNA vaccines.

scholarly journals Multimodal treatment strategies in Huntington’s disease

2021 ◽  
Vol 5 (2) ◽  
pp. 072-082
Author(s):  
Dutta Rajib
Keyword(s):  
Early Intervention ◽  
Neurodegenerative Disease ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Multimodal Treatment ◽  
Disease Onset ◽  
Genetic Diagnosis ◽  
Treatment Strategies ◽  
Emotional Lability ◽  
Made In

Huntington’s disease (HD) is an incurable neurodegenerative disease that causes involuntary movements, emotional lability, and cognitive dysfunction. HD symptoms usually develop between ages 30 and 50, but can appear as early as 2 or as late as 80 years. Currently no neuroprotective and neurorestorative interventions are available. Early multimodal intervention in HD is only possible if the genetic diagnosis is made early. Early intervention in HD is only possible if genetic diagnosis is made at the disease onset or when mild symptoms manifest. Growing evidence and understanding of HD pathomechanism has led researchers to new therapeutic targets. Here, in this article we will talk about the multimodal treatment strategies and recent advances made in this field which can be used to target the HD pathogenesis at its most proximal level.

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