The regulatory role of α-synuclein and parkin in neuronal cell apoptosis; possible implications for the pathogenesis of Parkinson’s disease

Long intergenic noncoding RNA-p21 (lincRNA-p21) has been reported to be increased in Parkinson’s disease (PD). However, the function and underlying mechanisms of lincRNA-p21 remain not clear. In order to explore the role of lincRNA-p21 in PD, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce in vivo PD model (C57BL/6 mice) and utilized N-methyl-4-phenylpyridinium (MPP+) to create in vitro PD model (SH-SY5Y cells). Results showed that the expression level of lincRNA-p21 was increased significantly in PD models. High abundance of lincRNA-p21 inhibited viability and promoted apoptosis markedly in SH-SY5Y cells treated with MPP+. Mechanistically, further experiments demonstrated that upregulation of lincRNA-p21 could sponge miR-1277-5p and indirectly increase the expression of α-synuclein to suppress viability and activate apoptosis in SH-SY5Y cells. In short, our study illustrated that lincRNA-p21/miR-1277-5p axis regulated viability and apoptosis in SH-SY5Y cells treated with MPP+ via targeting α-synuclein. LincRNA-p21 might be a novel target for PD.

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Original article The key role of sphingosine kinases in the molecular mechanism of neuronal cell survival and death in an experimental model of Parkinson’s disease

Folia Neuropathologica ◽

10.5114/fn.2014.45567 ◽

2014 ◽

Vol 3 ◽

pp. 260-269 ◽

Cited By ~ 27

Author(s):

Joanna A. Pyszko ◽

Joanna B. Strosznajder

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Survival ◽

Experimental Model ◽

Molecular Mechanism ◽

Neuronal Cell ◽

Sphingosine Kinases

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Infection and Risk of Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202279 ◽

2020 ◽

pp. 1-13

Author(s):

Richard J. Smeyne ◽

Alastair J Noyce ◽

Matthew Byrne ◽

Rodolfo Savica ◽

Connie Marras

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Viral Infections ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Alpha Synuclein ◽

Cytokines And Chemokines ◽

Genetic And Environmental Factors ◽

Neurotropic Effects

Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.

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