The Potential Role of Toll-Like Receptor 4 in Mediating Dopaminergic Cell Loss and Alpha-Synuclein Expression in the Acute MPTP Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 64 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Giuseppina Mariucci ◽  
Rita Pagiotti ◽  
Francesco Galli ◽  
Luigina Romani ◽  
Carmela Conte
2022 ◽  
Author(s):  
Min Hyung Seo ◽  
Sujung Yeo

Abstract Parkinson’s disease (PD) is known as the second most common neurodegenerative disease, which is caused by destruction of dopaminergic neurons in the substantia nigra (SN) of the brain; however, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) is considered an important factor in the pathogenesis of PD. In the current study, we investigated the association between PD and serine/arginine-rich protein specific kinase 3 (Srpk3) in MPTP-induced parkinsonism mice model and in SH-SY5Y cells treated with MPP+. Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) decreased and α-synuclein (α-syn) increased after 4 weeks of MPTP intoxication treatment. Dopaminergic cell reduction and α-syn increase were demonstrated by inhibiting Srpk3 expression by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn increase in SH-SY5Y cells treated with MPP+. These results suggest that the decrease in Srpk3 expression due to Srpk3 siRNA caused both a decrease in TH and an increase in α-syn. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to the pathogenesis of PD. Our results provide an avenue for understanding the role of Srpk3 during dopaminergic cell loss and α-syn increase in the SN. Furthermore, this study could support a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibited dopaminergic cell reduction.


RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.


2014 ◽  
Vol 146 (5) ◽  
pp. S-59
Author(s):  
Paula Perez-Pardo ◽  
Hidde Douna ◽  
Tom Wijnands ◽  
Sofia Lopes da Silva ◽  
Christopher B. Forsyth ◽  
...  

2019 ◽  
Vol 132 ◽  
pp. 104575 ◽  
Author(s):  
Debashis Dutta ◽  
Madhuchhanda Kundu ◽  
Susanta Mondal ◽  
Avik Roy ◽  
Samantha Ruehl ◽  
...  

2019 ◽  
Vol 47 (03) ◽  
pp. 527-539
Author(s):  
Sujung Yeo ◽  
Sabina Lim

Parkinson’s disease (PD), a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein ([Formula: see text]-syn) along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in [Formula: see text]-syn expression that is related with dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase. Moreover, acupuncture stimulation attenuated the increase in [Formula: see text]-syn. We identified that serum- and glucocorticoid-dependent kinase 1 (SGK1) is evidently downregulated in chronic MPTP-intoxication and acupuncture stimulation maintained SGK1 expression at levels similar to the control group. For an examination of the expression correlation between SGK1 and [Formula: see text]-syn, SH-SY5Y cells were knocked down with SGK1 siRNA then, the downregulation of dopaminergic cells and the increase in the expression of [Formula: see text]-syn were observed. Our findings indicate that the acupuncture-mediated inhibition in the [Formula: see text]-syn increase induced by MPTP may be responsible for modulating SGK1 expression.


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