Robust Dopaminergic Differentiation and Enhanced LPS-Induced Neuroinflammatory Response in Serum-Deprived Human SH-SY5Y Cells: Implication for Parkinson’s Disease

2020 ◽  
Author(s):  
Aram Niaz ◽  
Jocelyn Karunia ◽  
Mawj Mandwie ◽  
Kevin A. Keay ◽  
Giuseppe Musumeci ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroinflammatory Response ◽  
Dopaminergic Differentiation

scholarly journals Parkinson’s disease phenotypes in patient specific brain organoids are improved by HP-β-CD treatment

2019 ◽  
Author(s):  
Javier Jarazo ◽  
Kyriaki Barmpa ◽  
Isabel Rosety ◽  
Lisa M. Smits ◽  
Jonathan Arias-Fuenzalida ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gene Mutations ◽  
Neuronal Firing ◽  
Patient Specific ◽  
Specific Gene ◽  
Environmental Causes ◽  
Metabolic Properties ◽  
Biallelic Mutations ◽  
Dopaminergic Differentiation

AbstractThe etiology of Parkinson’s disease (PD) is only partially understood despite the fact that environmental causes, risk factors, and specific gene mutations are contributors to the disease. Biallelic mutations in the PTEN-induced putative kinase 1 (PINK1) gene involved in mitochondrial homeostasis, vesicle trafficking, and autophagy, are sufficient to cause PD. By comparing PD patient-derived cells, we show differences in their energetic profile, imbalanced proliferation, apoptosis, mitophagy, and a reduced differentiation efficiency to dopaminergic neurons compared to control cells. Using CRISPR/Cas9 gene editing, correction of a patient’s point mutation ameliorated the metabolic properties and neuronal firing rates but without reversing the differentiation phenotype. However, treatment with 2-Hydroxypropyl-β-Cyclodextrin (HP-β-CD) increased the mitophagy capacity of neurons leading to an improved dopaminergic differentiation of patient specific neurons in midbrain organoids. In conclusion, we show that treatment with a repurposed compound is sufficient for restoring dopaminergic differentiation of PD patient-derived cells.

scholarly journals Blood-Brain Barrier Therapeutics for Neurological Diseases

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Aarushi Sahni ◽  
Nicole Katchur
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Neuroinflammatory Response ◽  
Selective Filter ◽  
Blood Brain ◽  
The Brain

The Blood-Brain Barrier (BBB) is a highly selective filter responsible for allowing certain gases such as oxygen and lipid-soluble molecules to pass (Anand 2014). Its selectiveness makes it challenging for many therapeutics to combat Alzheimer’s and Parkinson’s disease with external drug therapies. Large-molecule drug therapies never pass the BBB while small-molecule drugs pass only about 5% of the time (Pardridge 2005). In Alzheimer’s disease, tight junctions between endothelial cells degrade, causing an unregulated accumulation of amyloid-β (Aβ) protein (Ramanathan 2015). Consequently, this leads to the formation of neurofibrillary tangles that cut off the nutrient supply to the brain cells and kill neurons (Ramanathan 2015). In Parkinson’s disease, astrocyte mutations cause a build-up of α-synuclein (αSyn) which affects the neuroinflammatory response and causes dysfunction in dopaminergic neurons (Booth 2017; Meade 2019). New drug therapies for Alzheimer’s and Parkinson’s continue to undergo trials; some such as FPS-ZM1 and tilavonemab for Alzheimer’s and Ravicti for Parkinson’s have shown promising results. In addition, similarities in dysfunction for both diseases and some types of cancer have sparked possibilities in retargeting cancer drugs to improve Alzheimer's and Parkinson’s pathologies. This review will summarize current therapeutic advancements for Alzheimer’s and Parkinson’s disease and their possible future contributions.

scholarly journals The natural functional biopolymer matrix demonstrates to be a promise for safe cell therapy in Parkinson’s disease

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Ana Carolina Irioda ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira Stricker ◽  
Nathalia Barth Oliverira ◽  
Nádia Nascimento da Rosa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Neuronal Differentiation ◽  
Neural Precursor ◽  
Metabolic Characteristics ◽  
Neuronal Precursors ◽  
The Difference ◽  
Dopaminergic Differentiation

Abstract Background Mesenchymal stem cells (MSCs) are undifferentiated cells and can be isolated from many tissues, including adipose tissue. MSCs neuronal differentiation ability has arisen interest in research with these cells in neurodegenerative diseases, such as Parkinson’s disease (PD). To differentiate MSCs in cells that produce dopamine that posteriorly potential to be a safe cell therapy for PD. Methods MSCs were isolated from adipose tissue, characterized by flow cytometry and trilineage differentiation, and cultivated seeded on natural functional biopolymer matrix (NFBX) to differentiate in neuronal precursors. Finally, a neural precursor was cultivated in the dopaminergic differentiation medium. The immunocytochemistry was performed with antibody anti-Nestin for precursor neural and antibodies anti-ß III-tubulin and hydroxylase tyrosine. Then, quantification of dopamine was made by the ELISA kit in the culture medium. Results The cytometric analysis of MSCs and the trilineage test to chondrocyte, osteocyte, and adipocyte demonstrated their pluripotency. Cells seeded and cultivated over NFBX have developed neurospheres, and their mechanical dissociated cells were Nestin positive. Dopaminergic differentiation was confirmed with positivity for ß-III tubulin and hydroxylase tyrosine. The dopamine concentration was very high in one sample (74.91 ng/mL). Without this sample, the media was 2.34 ± 2.13 ng/mL. The difference between dopamine concentrations was probably due to donors' metabolic characteristics. Conclusions The MSCs differentiated in neural precursor cells without genetic modification or growth factors, using only this NFBX. When these neural precursors were induced to differentiate, they were available to produce dopamine, demonstrating a functional neuronal differentiation.

scholarly journals The Parkinson’s-disease-associated mutation LRRK2-G2019S alters dopaminergic differentiation dynamics via NR2F1

Cell Reports ◽  
2021 ◽  
Vol 37 (3) ◽  
pp. 109864
Author(s):  
Jonas Walter ◽  
Silvia Bolognin ◽  
Suresh K. Poovathingal ◽  
Stefano Magni ◽  
Deborah Gérard ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lrrk2 G2019s ◽  
Dopaminergic Differentiation

scholarly journals Anti-Inflammatory Cytokine-Eluting Collagen Hydrogel Reduces the Host Immune Response to Dopaminergic Cell Transplants in a Rat Model of Parkinson's Disease

2021 ◽  
Author(s):  
Sílvia Cabré ◽  
Verónica Alamilla ◽  
Niamh Moriarty ◽  
Abhay Pandit ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Cytokine ◽  
Rat Striatum ◽  
In Vivo Evaluation ◽  
Neuroinflammatory Response ◽  
Collagen Hydrogel ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

In cell replacement approaches for Parkinson's disease, the intra-cerebral implantation of dopamine neuron-rich grafts generates a neuroinflammatory response to the grafted cells that contributes to its varied outcome. Thus, the aim of this study was to fabricate an anti-inflammatory cytokine-eluting collagen hydrogel capable of delivering IL-10 to the brain for reduction of the neuroinflammatory response to intra-cerebral cellular grafts. In vitro assessment revealed that crosslinker concentration affected the microstructure and gelation kinetics of the hydrogels and their IL-10 elution kinetics, but not their cytocompatibility or the functionality of the eluted IL-10. In vivo evaluation revealed that the hydrogels were capable of delivering and retaining IL-10 in the rat striatum, and reducing the neuroinflammatory (microglial) response to hydrogel-encapsulated grafts. In conclusion, IL-10-eluting collagen hydrogels may have beneficial anti-inflammatory effects in the context of cellular brain repair therapies for Parkinson's disease and should be investigated further.

Sign in / Sign up

Export Citation Format

Share Document