Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Directing the fate of mesenchymal stem cells (MSCs) to dopaminergic neurons has great importance in both biomedical studies and cell therapy of Parkinson's disease. We recently generated dopamine-secreting cells from human adipose tissue-derived stem cells (hADSCs) by exposing the cells to a growth factor cocktail composed of SHH, bFGF, FGF8 and BDNF in low-serum condition. In the current study, we induced the cells by the same dopaminergic inducing cocktail in serum-free B27-supplemented Neurobasal medium. ADSCs differentiated in both conditions expressed several neuronal and dopaminergic markers. However, there were higher gene expression levels under the serum-free condition. Higher levels of TUJ1 and TH proteins were also detected in the cells exposed to the dopaminergic-inducing cocktail under serum-free Neurobasal condition. TH protein was expressed in about 28% and 60% of the cells differentiated in the low-serum and serum-free Neurobasal media, respectively. Moreover, the cells exposed to the dopaminergic-inducing cocktail in the serum-free Neurobasal condition released a more significant amount of dopamine in response to KCl-induced depolarization. Altogether, these findings show a greater efficiency of the serum-free Neurobasal condition for growth factor-directed differentiation of hADSCs to functional dopamine-secreting cells which may be valuable for transplantation therapy of Parkinson's disease in future.
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PMID:Directed differentiation of human adipose tissue-derived stem cells to dopaminergic neurons in low-serum and serum-free conditions. 3125 59

Recent studies have elaborated on the concept that a number of microRNAs (miRNAs) have a potential effect on the pathogenesis and development of Parkinson's disease (PD). PD is recognized as a common progressive bradykinetic disorder that results from the death of dopaminergic neurons in the substantia nigra. The purpose of this study was to explore whether microRNA-124 (miR-124) affected dopamine receptor (DAR) expression and neuronal proliferation and apoptosis in the 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models of PD. The targeting relationship of miR-124 and EDN2 was confirmed through bioinformatic predictions and dual-luciferase reporter assay. The expression of miR-124 and EDN2 was altered to assess their effect on the expression of DAR in the substantia nigra and isolated neurons, as well as the neuronal proliferation and apoptosis rate. The obtained results implied that the treatments of miR-124 mimic and si-EDN2 resulted in elevated expressions of Glil, SHH, PTCH1, DAT, DRD1, and DRD2. However, these treatments facilitated neuronal proliferation and suppressed neuronal apoptosis, corresponding to reduced expression of caspase-3 and Bax, as well as increased levels of Bcl-2 expression. These results were discovered to be achieved through the activation of the Hedgehog signaling pathway. With this taken into account, our study demonstrated that miR-124 overexpression promoted DAR expression and neuronal proliferation and suppressed neuronal apoptosis by downregulating EDN2 via activating the Hedgehog signaling pathway.
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PMID:MicroRNA-124 Enhances Dopamine Receptor Expression and Neuronal Proliferation in Mouse Models of Parkinson's Disease via the Hedgehog Signaling Pathway by Targeting EDN2. 3145 17

Electroactive scaffolds derived from carbohydrate hydrogels were synthesized, resulting in a large shift in the conductivity of chitosan (CS) from 10-6 S/cm to about 10-3 S/cm, assigned to CS-oligoaniline. Several analyses including UV-vis spectroscopy and cyclic voltammetry were performed, before examining the carbohydrate-based scaffolds for their ability to recapitulate the neural tissue microenvironment. Good conductivity and resemblance of the modulus to soft tissue of the optimized hydrogels led to appropriate cellular activity and neural regeneration. The loss of dopaminergic neurons as the prominent source of dopamine in the central nervous system results in the deterioration of multiple brain functions such as voluntary movement and behavioral processes. To overcome this, olfactory ecto-mesenchymal stem cells (OE-MSCs) were induced to differentiate into dopaminergic neuron-like cells on hydrogels through a monolayer arrangement cell culture by using cocktail neurotrophic factors including sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF), glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF). The differentiation capacity of a series of OE-MSCs on the conductive hydrogel was evaluated by real-time PCR, immunocytochemistry and flow cytometry, and the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) neural and dopaminergic markers. The results of this study represent the first steps in designing and implementing advanced platforms based on conductive polysaccharide hydrogels for neural disorder therapies, such as the treatment of Parkinson's disease.
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PMID:Conductive hydrogels based on agarose/alginate/chitosan for neural disorder therapy. 3147 54

The mesodiencephalic dopaminergic (mdDA) group of neurons comprises molecularly distinct subgroups, of which the substantia nigra (SN) and ventral tegmental area (VTA) are the best known, due to the selective degeneration of the SN during Parkinson's disease. However, although significant research has been conducted on the molecular build-up of these subsets, much is still unknown about how these subsets develop and which factors are involved in this process. In this review, we aim to describe the life of an mdDA neuron, from specification in the floor plate to differentiation into the different subsets. All mdDA neurons are born in the mesodiencephalic floor plate under the influence of both SHH-signaling, important for floor plate patterning, and WNT-signaling, involved in establishing the progenitor pool and the start of the specification of mdDA neurons. Furthermore, transcription factors, like Ngn2, Ascl1, Lmx1a, and En1, and epigenetic factors, like Ezh2, are important in the correct specification of dopamine (DA) progenitors. Later during development, mdDA neurons are further subdivided into different molecular subsets by, amongst others, Otx2, involved in the specification of subsets in the VTA, and En1, Pitx3, Lmx1a, and WNT-signaling, involved in the specification of subsets in the SN. Interestingly, factors involved in early specification in the floor plate can serve a dual function and can also be involved in subset specification. Besides the mdDA group of neurons, other systems in the embryo contain different subsets, like the immune system. Interestingly, many factors involved in the development of mdDA neurons are similarly involved in immune system development and vice versa. This indicates that similar mechanisms are used in the development of these systems, and that knowledge about the development of the immune system may hold clues for the factors involved in the development of mdDA neurons, which may be used in culture protocols for cell replacement therapies.
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PMID:Acquisition of the Midbrain Dopaminergic Neuronal Identity. 3262 12


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