Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease
Abstract Peptides and their mimetics are increasingly recognised as drug-like molecules, particularly for intracellular protein-protein interactions too large for inhibition by small molecules, and inaccessible to larger biologics. In the past two decades, evidence associating the misfolding and agg...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13024-023-00675-8 |
| _version_ | 1797629973705523200 |
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| author | Scott G. Allen Richard M. Meade Lucy L. White Stenner Jody M. Mason |
| author_facet | Scott G. Allen Richard M. Meade Lucy L. White Stenner Jody M. Mason |
| author_sort | Scott G. Allen |
| collection | DOAJ |
| description | Abstract Peptides and their mimetics are increasingly recognised as drug-like molecules, particularly for intracellular protein-protein interactions too large for inhibition by small molecules, and inaccessible to larger biologics. In the past two decades, evidence associating the misfolding and aggregation of alpha-synuclein strongly implicates this protein in disease onset and progression of Parkinson’s disease and related synucleinopathies. The subsequent formation of toxic, intracellular, Lewy body deposits, in which alpha-synuclein is a major component, is a key diagnostic hallmark of the disease. To reach their therapeutic site of action, peptides must both cross the blood-brain barrier and enter dopaminergic neurons to prevent the formation of these intracellular inclusions. In this review, we describe and summarise the current efforts made in the development of peptides and their mimetics to directly engage with alpha-synuclein with the intention of modulating aggregation, and importantly, toxicity. This is a rapidly expanding field with great socioeconomic impact; these molecules harbour significant promise as therapeutics, or as early biomarkers during prodromal disease stages, or both. As these are age-dependent conditions, an increasing global life expectancy means disease prevalence is rising. No current treatments exist to either prevent or slow disease progression. It is therefore crucial that drugs are developed for these conditions before health care and social care capacities become overrun. |
| first_indexed | 2024-03-11T11:01:26Z |
| format | Article |
| id | doaj.art-aed8144564684655ade3c7b5783c548d |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-03-11T11:01:26Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-aed8144564684655ade3c7b5783c548d2023-11-12T12:30:05ZengBMCMolecular Neurodegeneration1750-13262023-11-0118111510.1186/s13024-023-00675-8Peptide-based approaches to directly target alpha-synuclein in Parkinson’s diseaseScott G. Allen0Richard M. Meade1Lucy L. White Stenner2Jody M. Mason3Department of Life Sciences, University of BathDepartment of Life Sciences, University of BathDepartment of Life Sciences, University of BathDepartment of Life Sciences, University of BathAbstract Peptides and their mimetics are increasingly recognised as drug-like molecules, particularly for intracellular protein-protein interactions too large for inhibition by small molecules, and inaccessible to larger biologics. In the past two decades, evidence associating the misfolding and aggregation of alpha-synuclein strongly implicates this protein in disease onset and progression of Parkinson’s disease and related synucleinopathies. The subsequent formation of toxic, intracellular, Lewy body deposits, in which alpha-synuclein is a major component, is a key diagnostic hallmark of the disease. To reach their therapeutic site of action, peptides must both cross the blood-brain barrier and enter dopaminergic neurons to prevent the formation of these intracellular inclusions. In this review, we describe and summarise the current efforts made in the development of peptides and their mimetics to directly engage with alpha-synuclein with the intention of modulating aggregation, and importantly, toxicity. This is a rapidly expanding field with great socioeconomic impact; these molecules harbour significant promise as therapeutics, or as early biomarkers during prodromal disease stages, or both. As these are age-dependent conditions, an increasing global life expectancy means disease prevalence is rising. No current treatments exist to either prevent or slow disease progression. It is therefore crucial that drugs are developed for these conditions before health care and social care capacities become overrun.https://doi.org/10.1186/s13024-023-00675-8Alpha-SynucleinSynucleinopathiesParkinson’s DiseasePeptide therapeuticsPeptidomimetics |
| spellingShingle | Scott G. Allen Richard M. Meade Lucy L. White Stenner Jody M. Mason Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease Molecular Neurodegeneration Alpha-Synuclein Synucleinopathies Parkinson’s Disease Peptide therapeutics Peptidomimetics |
| title | Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease |
| title_full | Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease |
| title_fullStr | Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease |
| title_full_unstemmed | Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease |
| title_short | Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease |
| title_sort | peptide based approaches to directly target alpha synuclein in parkinson s disease |
| topic | Alpha-Synuclein Synucleinopathies Parkinson’s Disease Peptide therapeutics Peptidomimetics |
| url | https://doi.org/10.1186/s13024-023-00675-8 |
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