ArticleMolecular neurobiology2018
Alpha-synuclein alters differently gene expression of Sirts, PARPs and other stress response proteins: implications for neurodegenerative disorders.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- FoxO1 Alleviates the Mitochondrial ROS Levels Induced by α-Synuclein Preformed Fibrils in BV-2 Microglial Cells.Inflammation · 2025Article
- Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.CNS neuroscience & therapeutics · 2024Article
- Specific and shared biological functions of PARP2 - is PARP2 really a lil' brother of PARP1?Expert reviews in molecular medicine · 2024Review
- Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies.Neural regeneration research · 2023Article
- Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer's and Parkinson's diseases.Biology of sex differences · 2023Article
- SIRT1 activation and its circadian clock control: a promising approach against (frailty in) neurodegenerative disorders.Aging clinical and experimental research · 2022Review
- The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson's Disease.Biomolecules · 2022Article
- The role of Gadd45b in neurologic and neuropsychiatric disorders: An overview.Frontiers in molecular neuroscience · 2022Review
- Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values.Lipids in health and disease · 2021Article
- Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson's Disease.International journal of molecular sciences · 2021Review
- Sirtuin 3 mRNA Expression is Downregulated in the Brain Tissues of Alzheimer's Disease Patients: A Bioinformatic and Data Mining Approach.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Review
- SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases.Frontiers in pharmacology · 2020Review
- Small molecules as therapeutic drugs for Alzheimer's disease.Molecular and cellular neurosciences · 2019Review
- Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics.International journal of molecular sciences · 2019Article
- The Role of Lipids in Parkinson's Disease.Cells · 2019Review
- Emerging Role of Sirtuin 2 in Parkinson's Disease.Frontiers in aging neuroscience · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. It's assumed that ASN plays an important role in the pathogenesis of Parkinson's and Alzheimer's disease. However, the molecular mechanism of ASN toxicity has not been elucidated. This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. Our results indicate that eASN enhanced the free radicals level, decreased mitochondria membrane potential, cells viability and activated cells' death. Concomitantly eASN activated expression of antioxidative proteins (Sod2, Gpx4, Gadd45b) and DNA-bound Parp2 and Parp3. Moreover, eASN upregulated expression of Sirt3 and Sirt5, but downregulated of Sirt1, which plays an important role in cell metabolism including Aβ precursor protein (APP) processing. eASN downregulated gene expression of APP alpha secretase (Adam10) and metalloproteinases Mmp2, Mmp10 but upregulated Mmp11. Additionally, expression and activity of pro-survival sphingosine kinase 1 (Sphk1), Akt kinase and anti-apoptotic protein Bcl2 were inhibited. Moreover, higher expression of pro-apoptotic protein Bax and enhancement of apoptotic cells' death were observed. Summarizing, eASN significantly modulates transcription of Sirts and enzymes involved in APP/Aβ metabolism and through these mechanisms eASN toxicity may be enhanced. The inhibition of Sphk1 and Akt by eASN may lead to disturbances of survival pathways. These results suggest that eASN through alteration of transcription and by inhibition of pro-survival kinases may play important pathogenic role in neurodegenerative disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.