scholarly journals Synthesis and Biological Evaluation of Novel Selenyl and Sulfur-l-Dopa Derivatives as Potential Anti-Parkinson’s Disease Agents

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 239 ◽  
Author(s):  
Di Stefano ◽  
Marinelli ◽  
Eusepi ◽  
Ciulla ◽  
Fulle ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Line ◽  
Neuroblastoma Cell ◽  
Biological Evaluation ◽  
Neuroblastoma Cell Line ◽  
Biological Data ◽  
Substantia Nigra Pars Compacta ◽  
Plasma Stability ◽  
Synthesis And Biological Evaluation

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons at level of substantia nigra pars compacta. To date, there is no cure for this pathology, except for some drugs able to alleviate the symptoms of PD. In this paper we report the synthesis and biological evaluation of novel sulfur- and selenyl-l-Dopa (LD) derivatives (SP1–6) obtained through the amide junction between the amino group of LD and carboxylic moiety of sulfur- and selenyl-organic compounds, which are commercially available. Biological activity was evaluated on human undifferentiated and retinoic acid/phorbol myristyl acetate (RA/PMA)-differentiated SY-SH5Y neuroblastoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activity against oxidative stress was measured using nitroblue tetrazolium (NBT) and 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) assays. Finally, physico-chemical characterization and plasma stability studies of SP1–6 were also performed. Biological data revealed that SP6 has a significant protective action against the neurotoxic action of 6-hydroxydopamine (6-OHDA) and H2O2 in a RA/PMA-differentiated SY-SH5Y neuroblastoma cell line that proved to be an effective antioxidant and protective compound. SP6, endowed with a lipophilic nature, low molecular weight, and plasma stability, can easily cross biological membranes via passive diffusion such as through the blood–brain barrier. SP6 has great potential for developing novel pharmacological approach for neurodegenerative diseases, such as PD. Further studies will help define its exact antioxidant mechanism and determine whether the neuroprotective action is mediated or modulated by glutathione peroxidase (GPx).

scholarly journals Systems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 1154 ◽  
Author(s):  
Abhimanyu Krishna ◽  
Maria Biryukov ◽  
Christophe Trefois ◽  
Paul MA Antony ◽  
Rene Hussong ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line

scholarly journals Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line

2020 ◽  
Vol 21 (12) ◽  
pp. 4455
Author(s):  
Rong-Tzong Tsai ◽  
Chia-Wen Tsai ◽  
Shih-Ping Liu ◽  
Jia-Xin Gao ◽  
Yun-Hua Kuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Cell Line ◽  
Ubiquitin Proteasome System ◽  
Substantia Nigra Pars Compacta ◽  
Neuron Damage ◽  
6 Hydroxydopamine

The movement disorder Parkinson’s disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Sophora flavescens Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in Caenorhabditis elegans and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% (p < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing PINK1/parkin expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.

Synthesis and biological evaluation of pentacyclo[5.4.0.02,6.03,10.05,9]undecane derivatives as potential therapeutic agents in Parkinson's disease

2004 ◽  
Vol 12 (7) ◽  
pp. 1799-1806 ◽  
Author(s):  
Werner J Geldenhuys ◽  
Sarel F Malan ◽  
Thangaraju Murugesan ◽  
Cornelis J Van der Schyf ◽  
Jeffrey R Bloomquist
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biological Evaluation ◽  
Therapeutic Agents ◽  
Synthesis And Biological Evaluation

scholarly journals CRISPR/Cas9 Mediated-Disruption of ZNF543 Gene: An Approach Towards Discovering Its Relation to TRIM28 Gene in Parkinson's Disease

2021 ◽  
Author(s):  
Mohammad Hashemabadi ◽  
Hosseinali Sasan ◽  
Mojdeh Amandadi ◽  
Keyvan Esmaeilzadeh-Salestani ◽  
Saeed Esmaeili-Mahani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroblastoma Cell ◽  
Regulatory Region ◽  
Gene Mutations ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Genetic Studies

Abstract Genetic studies of familial forms of Parkinson’s disease (PD) have shown that the ZNF543 gene is a candidate gene that operates relevant to this disease. However, until now there is no evidence for ZNF543 gene function in PD, and mechanisms resulting from its mutation had not been elucidated. Given the same genetic location of the ZNF543 gene with TRIM28 and effects of both of them on PD pathogenesis, we surmised that ZNF543 may act as a transcription factor for TRIM28 gene expression. By knocking out the ZNF543 gene via the CRISPR/Cas9 editing platform, we assessed the functional effect of loss of expression of this gene on TRIM28 gene expression. Four sgRNAs with different PAM sequences were designed against two parts of the regulatory region of ZNF543 gene, and highly efficient disruption of ZNF543 expression in human neuroblastoma cell line was evaluated by polymerase chain reaction and T7 endonuclease assay. Moreover, evaluation of TRIM28 gene expression in ZNF543-knocked-out cells indicated a significant increase of TRIM28 gene expression, suggesting that ZNF543 probably regulates the expression of TRIM28. This approach offers a window into pinpointing the mechanism by which ZNF543 gene mutations mediate PD pathogenicity.

The mechanistic role of thymoquinone in Parkinson's disease: focus on neuroprotection in pre-clinical studies

2021 ◽  
Vol 14 ◽  
Author(s):  
Mohammad Najim Uddin ◽  
Mohammad Injamul Hoq ◽  
Israt Jahan ◽  
Shafayet Ahmed Siddiqui ◽  
Chayan Dhar Clinton ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Studies ◽  
Nigella Sativa ◽  
Biological Effects ◽  
Neuroprotective Activity ◽  
Substantia Nigra Pars Compacta ◽  
Movement Difficulties

: Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.

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