Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases
Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, are a class of diseases that lead to dysfunction of cognition and mobility. Aggregates of misfolded proteins such as β-amyloid, tau, α-synuclein, and polyglutamates are known to be among the mai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/11/7/607 |
| _version_ | 1827688876635848704 |
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| author | Soonsil Hyun Dongyun Shin |
| author_facet | Soonsil Hyun Dongyun Shin |
| author_sort | Soonsil Hyun |
| collection | DOAJ |
| description | Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, are a class of diseases that lead to dysfunction of cognition and mobility. Aggregates of misfolded proteins such as β-amyloid, tau, α-synuclein, and polyglutamates are known to be among the main causes of neurodegenerative diseases; however, they are considered to be some of the most challenging drug targets because they cannot be modulated by conventional small-molecule agents. Recently, the degradation of target proteins by small molecules has emerged as a new therapeutic modality and has garnered the interest of the researchers in the pharmaceutical industry. Bifunctional molecules that recruit target proteins to a cellular protein degradation machinery, such as the ubiquitin–proteasome system and autophagy–lysosome pathway, have been designed. The representative targeted protein degradation technologies include molecular glues, proteolysis-targeting chimeras, hydrophobic tagging, autophagy-targeting chimeras, and autophagosome-tethering compounds. Although these modalities have been shown to degrade many disease-related proteins, such technologies are expected to be potentially important for neurogenerative diseases caused by protein aggregation. Herein, we review the recent progress in chemical-mediated targeted protein degradation toward the discovery of drugs for neurogenerative diseases. |
| first_indexed | 2024-03-10T10:06:48Z |
| format | Article |
| id | doaj.art-b428abff1aac451c8a65e0702c9d94dd |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T10:06:48Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-b428abff1aac451c8a65e0702c9d94dd2023-11-22T01:31:28ZengMDPI AGLife2075-17292021-06-0111760710.3390/life11070607Chemical-Mediated Targeted Protein Degradation in Neurodegenerative DiseasesSoonsil Hyun0Dongyun Shin1Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, Yeonsu-gu, Incheon 21936, KoreaGachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, Yeonsu-gu, Incheon 21936, KoreaNeurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, are a class of diseases that lead to dysfunction of cognition and mobility. Aggregates of misfolded proteins such as β-amyloid, tau, α-synuclein, and polyglutamates are known to be among the main causes of neurodegenerative diseases; however, they are considered to be some of the most challenging drug targets because they cannot be modulated by conventional small-molecule agents. Recently, the degradation of target proteins by small molecules has emerged as a new therapeutic modality and has garnered the interest of the researchers in the pharmaceutical industry. Bifunctional molecules that recruit target proteins to a cellular protein degradation machinery, such as the ubiquitin–proteasome system and autophagy–lysosome pathway, have been designed. The representative targeted protein degradation technologies include molecular glues, proteolysis-targeting chimeras, hydrophobic tagging, autophagy-targeting chimeras, and autophagosome-tethering compounds. Although these modalities have been shown to degrade many disease-related proteins, such technologies are expected to be potentially important for neurogenerative diseases caused by protein aggregation. Herein, we review the recent progress in chemical-mediated targeted protein degradation toward the discovery of drugs for neurogenerative diseases.https://www.mdpi.com/2075-1729/11/7/607neurodegenerative diseaseprotein degradationdrug designubiquitin-proteasome systemautophagyprotac |
| spellingShingle | Soonsil Hyun Dongyun Shin Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases Life neurodegenerative disease protein degradation drug design ubiquitin-proteasome system autophagy protac |
| title | Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases |
| title_full | Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases |
| title_fullStr | Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases |
| title_full_unstemmed | Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases |
| title_short | Chemical-Mediated Targeted Protein Degradation in Neurodegenerative Diseases |
| title_sort | chemical mediated targeted protein degradation in neurodegenerative diseases |
| topic | neurodegenerative disease protein degradation drug design ubiquitin-proteasome system autophagy protac |
| url | https://www.mdpi.com/2075-1729/11/7/607 |
| work_keys_str_mv | AT soonsilhyun chemicalmediatedtargetedproteindegradationinneurodegenerativediseases AT dongyunshin chemicalmediatedtargetedproteindegradationinneurodegenerativediseases |