Dopaminergic cell death in Parkinson’s disease: a role of iron?

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

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α-Synuclein Enhances Cadmium Uptake and Neurotoxicity via Oxidative Stress and Caspase Activated Cell Death Mechanisms in a Dopaminergic Cell Model of Parkinson’s Disease

Neurotoxicity Research ◽

10.1007/s12640-017-9725-x ◽

2017 ◽

Vol 32 (2) ◽

pp. 231-246 ◽

Cited By ~ 2

Author(s):

Weelic Chong ◽

Jessica Jiménez ◽

Matthew McIIvin ◽

Mak A. Saito ◽

Gunnar F. Kwakye

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Cell Model ◽

Cadmium Uptake ◽

Dopaminergic Cell ◽

Cell Death Mechanisms

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Microglia mediated dopaminergic cell death in the substantia nigra: A new animal model for Parkinson's disease

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(98)90128-9 ◽

1998 ◽

Vol 25 ◽

pp. S44 ◽

Cited By ~ 1

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Model ◽

Cell Death ◽

Substantia Nigra ◽

Dopaminergic Cell

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Association Between Decreased Srpk3 Expression And An Increase In Substantia Nigra Alpha-Synuclein Levels In An MPTP-Induced Parkinson’s Disease Mouse Model

10.21203/rs.3.rs-1207279/v1 ◽

2022 ◽

Author(s):

Min Hyung Seo ◽

Sujung Yeo

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Dopaminergic Neurons ◽

Cell Loss ◽

Alpha Synuclein ◽

Mice Model ◽

Dopaminergic Cell ◽

The Brain

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.

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