Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies
α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the <i>SNCA</i> gene. Missense mutations and gene duplications in the <i>SNCA</i> gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6216 |
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| author | Ichiro Kawahata David I. Finkelstein Kohji Fukunaga |
| author_facet | Ichiro Kawahata David I. Finkelstein Kohji Fukunaga |
| author_sort | Ichiro Kawahata |
| collection | DOAJ |
| description | α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the <i>SNCA</i> gene. Missense mutations and gene duplications in the <i>SNCA</i> gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. Consequently, this review focuses on the pathogenic impact of α-synuclein phosphorylation and its kinases during the neurodegeneration process in α-synucleinopathy. |
| first_indexed | 2024-03-10T01:13:56Z |
| format | Article |
| id | doaj.art-315eb0a65332473e8fe99dc86c1e6058 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:13:56Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-315eb0a65332473e8fe99dc86c1e60582023-11-23T14:11:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012311621610.3390/ijms23116216Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-SynucleinopathiesIchiro Kawahata0David I. Finkelstein1Kohji Fukunaga2Department of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, JapanFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC 3010, AustraliaDepartment of CNS Drug Innovation, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japanα-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the <i>SNCA</i> gene. Missense mutations and gene duplications in the <i>SNCA</i> gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. Consequently, this review focuses on the pathogenic impact of α-synuclein phosphorylation and its kinases during the neurodegeneration process in α-synucleinopathy.https://www.mdpi.com/1422-0067/23/11/6216α-synucleinphosphorylationParkinson’s diseasedementia with Lewy bodiesmultiple system atrophyα-synucleinopathy |
| spellingShingle | Ichiro Kawahata David I. Finkelstein Kohji Fukunaga Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies International Journal of Molecular Sciences α-synuclein phosphorylation Parkinson’s disease dementia with Lewy bodies multiple system atrophy α-synucleinopathy |
| title | Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies |
| title_full | Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies |
| title_fullStr | Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies |
| title_full_unstemmed | Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies |
| title_short | Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies |
| title_sort | pathogenic impact of α synuclein phosphorylation and its kinases in α synucleinopathies |
| topic | α-synuclein phosphorylation Parkinson’s disease dementia with Lewy bodies multiple system atrophy α-synucleinopathy |
| url | https://www.mdpi.com/1422-0067/23/11/6216 |
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