The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses
The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/8338 |
| _version_ | 1797525444009918464 |
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| author | Asad Jan Nádia Pereira Gonçalves Christian Bjerggaard Vaegter Poul Henning Jensen Nelson Ferreira |
| author_facet | Asad Jan Nádia Pereira Gonçalves Christian Bjerggaard Vaegter Poul Henning Jensen Nelson Ferreira |
| author_sort | Asad Jan |
| collection | DOAJ |
| description | The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies. |
| first_indexed | 2024-03-10T09:13:58Z |
| format | Article |
| id | doaj.art-5b247a9623ea46e38eda064d88427cec |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:13:58Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5b247a9623ea46e38eda064d88427cec2023-11-22T05:46:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012215833810.3390/ijms22158338The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and HypothesesAsad Jan0Nádia Pereira Gonçalves1Christian Bjerggaard Vaegter2Poul Henning Jensen3Nelson Ferreira4Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDanish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDanish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDanish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDanish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkThe pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.https://www.mdpi.com/1422-0067/22/15/8338Parkinson’s diseasealpha-synucleinprion-likeneurodegeneration |
| spellingShingle | Asad Jan Nádia Pereira Gonçalves Christian Bjerggaard Vaegter Poul Henning Jensen Nelson Ferreira The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses International Journal of Molecular Sciences Parkinson’s disease alpha-synuclein prion-like neurodegeneration |
| title | The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses |
| title_full | The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses |
| title_fullStr | The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses |
| title_full_unstemmed | The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses |
| title_short | The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses |
| title_sort | prion like spreading of alpha synuclein in parkinson s disease update on models and hypotheses |
| topic | Parkinson’s disease alpha-synuclein prion-like neurodegeneration |
| url | https://www.mdpi.com/1422-0067/22/15/8338 |
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