An Update on the Critical Role of α-Synuclein in Parkinson’s Disease and Other Synucleinopathies: from Tissue to Cellular and Molecular Levels
| العنوان: | An Update on the Critical Role of α-Synuclein in Parkinson’s Disease and Other Synucleinopathies: from Tissue to Cellular and Molecular Levels |
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| المؤلفون: | Abel Santamaría, Carolina Campos, Michael Aschner, Elizabeth Hernández-Pérez, Iris N. Serratos |
| المصدر: | Molecular Neurobiology. 59:620-642 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Neurons, Synucleinopathies, Chemistry, Endoplasmic reticulum, Neuroscience (miscellaneous), Brain, Cellular homeostasis, Parkinson Disease, Protein degradation, Golgi apparatus, Cell biology, Vesicular transport protein, Cellular and Molecular Neuroscience, Cytosol, symbols.namesake, Neurology, alpha-Synuclein, symbols, Animals, Humans, Cytoskeleton |
| الوصف: | The aggregation of alpha-synuclein (α-Syn) plays a critical role in the development of Parkinson's disease (PD) and other synucleinopathies. α-Syn, which is encoded by the SNCA gene, is a lysine-rich soluble amphipathic protein normally expressed in neurons. Located in the cytosolic domain, this protein has the ability to remodel itself in plasma membranes, where it assumes an alpha-helix conformation. However, the protein can also adopt another conformation rich in cross-beta sheets, undergoing mutations and post-translational modifications, then leading the protein to an unusual aggregation in the form of Lewy bodies (LB), which are cytoplasmic inclusions constituted predominantly by α-Syn. Pathogenic mechanisms affecting the structural and functional stability of α-Syn - such as endoplasmic reticulum stress, Golgi complex fragmentation, disfunctional protein degradation systems, aberrant interactions with mitochondrial membranes and nuclear DNA, altered cytoskeleton dynamics, disrupted neuronal plasmatic membrane, dysfunctional vesicular transport, and formation of extracellular toxic aggregates - contribute all to the pathogenic progression of PD and synucleinopathies. In this review, we describe the collective knowledge on this topic and provide an update on the critical role of α-Syn aggregates, both at the cellular and molecular levels, in the deregulation of organelles affecting the cellular homeostasis and leading to neuronal cell death in PD and other synucleinopathies. |
| تدمد: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-021-02596-3 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f9d9e4217f9d6f6326415d97abe29d6 https://doi.org/10.1007/s12035-021-02596-3 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....5f9d9e4217f9d6f6326415d97abe29d6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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| DOI: | 10.1007/s12035-021-02596-3 |