Structural and Functional Insights into α-Synuclein Fibril Polymorphism
Abnormal accumulation of aggregated α-synuclein (α-Syn) is seen in a variety of neurodegenerative diseases, including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), Parkinson’s disease dementia (PDD), and even subsets of Alzheimer’s disease (AD) showing Lewy-...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/10/1419 |
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| author | Surabhi Mehra Laxmikant Gadhe Riya Bera Ajay Singh Sawner Samir K. Maji |
| author_facet | Surabhi Mehra Laxmikant Gadhe Riya Bera Ajay Singh Sawner Samir K. Maji |
| author_sort | Surabhi Mehra |
| collection | DOAJ |
| description | Abnormal accumulation of aggregated α-synuclein (α-Syn) is seen in a variety of neurodegenerative diseases, including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), Parkinson’s disease dementia (PDD), and even subsets of Alzheimer’s disease (AD) showing Lewy-body-like pathology. These synucleinopathies exhibit differences in their clinical and pathological representations, reminiscent of prion disorders. Emerging evidence suggests that α-Syn self-assembles and polymerizes into conformationally diverse polymorphs in vitro and in vivo, similar to prions. These α-Syn polymorphs arising from the same precursor protein may exhibit strain-specific biochemical properties and the ability to induce distinct pathological phenotypes upon their inoculation in animal models. In this review, we discuss clinical and pathological variability in synucleinopathies and several aspects of α-Syn fibril polymorphism, including the existence of high-resolution molecular structures and brain-derived strains. The current review sheds light on the recent advances in delineating the structure–pathogenic relationship of α-Syn and how diverse α-Syn molecular polymorphs contribute to the existing clinical heterogeneity in synucleinopathies. |
| first_indexed | 2024-03-10T06:42:17Z |
| format | Article |
| id | doaj.art-447d3d2097784b9482bf2f277c306c21 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T06:42:17Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-447d3d2097784b9482bf2f277c306c212023-11-22T17:33:17ZengMDPI AGBiomolecules2218-273X2021-09-011110141910.3390/biom11101419Structural and Functional Insights into α-Synuclein Fibril PolymorphismSurabhi Mehra0Laxmikant Gadhe1Riya Bera2Ajay Singh Sawner3Samir K. Maji4Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, IndiaDepartment of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, IndiaDepartment of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, IndiaDepartment of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, IndiaDepartment of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, IndiaAbnormal accumulation of aggregated α-synuclein (α-Syn) is seen in a variety of neurodegenerative diseases, including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), Parkinson’s disease dementia (PDD), and even subsets of Alzheimer’s disease (AD) showing Lewy-body-like pathology. These synucleinopathies exhibit differences in their clinical and pathological representations, reminiscent of prion disorders. Emerging evidence suggests that α-Syn self-assembles and polymerizes into conformationally diverse polymorphs in vitro and in vivo, similar to prions. These α-Syn polymorphs arising from the same precursor protein may exhibit strain-specific biochemical properties and the ability to induce distinct pathological phenotypes upon their inoculation in animal models. In this review, we discuss clinical and pathological variability in synucleinopathies and several aspects of α-Syn fibril polymorphism, including the existence of high-resolution molecular structures and brain-derived strains. The current review sheds light on the recent advances in delineating the structure–pathogenic relationship of α-Syn and how diverse α-Syn molecular polymorphs contribute to the existing clinical heterogeneity in synucleinopathies.https://www.mdpi.com/2218-273X/11/10/1419α-synucleinamyloidpolymorphssynucleinopathies |
| spellingShingle | Surabhi Mehra Laxmikant Gadhe Riya Bera Ajay Singh Sawner Samir K. Maji Structural and Functional Insights into α-Synuclein Fibril Polymorphism Biomolecules α-synuclein amyloid polymorphs synucleinopathies |
| title | Structural and Functional Insights into α-Synuclein Fibril Polymorphism |
| title_full | Structural and Functional Insights into α-Synuclein Fibril Polymorphism |
| title_fullStr | Structural and Functional Insights into α-Synuclein Fibril Polymorphism |
| title_full_unstemmed | Structural and Functional Insights into α-Synuclein Fibril Polymorphism |
| title_short | Structural and Functional Insights into α-Synuclein Fibril Polymorphism |
| title_sort | structural and functional insights into α synuclein fibril polymorphism |
| topic | α-synuclein amyloid polymorphs synucleinopathies |
| url | https://www.mdpi.com/2218-273X/11/10/1419 |
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