Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases
Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β, Tau, and α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). In add...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co. Ltd.
2023-07-01
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| Series: | Fundamental Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667325822004228 |
| _version_ | 1797774762786684928 |
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| author | Shenqing Zhang Hui Dong Jiang Bian Dan Li Cong Liu |
| author_facet | Shenqing Zhang Hui Dong Jiang Bian Dan Li Cong Liu |
| author_sort | Shenqing Zhang |
| collection | DOAJ |
| description | Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β, Tau, and α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). In addition, various post-translational modifications (PTMs) have been identified on pathological amyloid proteins and are subjected to change during disease progression. Given the central role of amyloid proteins in NDs, tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of NDs. In this review, we summarize two major strategies for targeting amyloid aggregates, with a focus on the trials in AD diagnosis. The first strategy is a positron emission tomography (PET) scan of protein aggregation in the brain. We mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid fibrils. The second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and plasma. We discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical diagnosis. Finally, we point out the potential technical challenges of these two strategies, and outline other potential strategies, as well as a combination of multiple strategies, for molecular diagnosis of NDs. |
| first_indexed | 2024-03-12T22:25:56Z |
| format | Article |
| id | doaj.art-a8d08d8d0d174b5388290b377dfe7eb1 |
| institution | Directory Open Access Journal |
| issn | 2667-3258 |
| language | English |
| last_indexed | 2024-03-12T22:25:56Z |
| publishDate | 2023-07-01 |
| publisher | KeAi Communications Co. Ltd. |
| record_format | Article |
| series | Fundamental Research |
| spelling | doaj.art-a8d08d8d0d174b5388290b377dfe7eb12023-07-22T04:53:06ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582023-07-0134505519Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseasesShenqing Zhang0Hui Dong1Jiang Bian2Dan Li3Cong Liu4Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, ChinaInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of the Chinese Academy of Sciences, Beijing 100049, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, ChinaBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240, China.Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China; Corresponding author.Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β, Tau, and α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD). In addition, various post-translational modifications (PTMs) have been identified on pathological amyloid proteins and are subjected to change during disease progression. Given the central role of amyloid proteins in NDs, tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of NDs. In this review, we summarize two major strategies for targeting amyloid aggregates, with a focus on the trials in AD diagnosis. The first strategy is a positron emission tomography (PET) scan of protein aggregation in the brain. We mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid fibrils. The second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and plasma. We discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical diagnosis. Finally, we point out the potential technical challenges of these two strategies, and outline other potential strategies, as well as a combination of multiple strategies, for molecular diagnosis of NDs.http://www.sciencedirect.com/science/article/pii/S2667325822004228Amyloid aggregationNeurodegenerative diseasesClinical diagnosisAlzheimer's diseasePositron emission tomography (PET) tracerTau |
| spellingShingle | Shenqing Zhang Hui Dong Jiang Bian Dan Li Cong Liu Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases Fundamental Research Amyloid aggregation Neurodegenerative diseases Clinical diagnosis Alzheimer's disease Positron emission tomography (PET) tracer Tau |
| title | Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| title_full | Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| title_fullStr | Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| title_full_unstemmed | Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| title_short | Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| title_sort | targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases |
| topic | Amyloid aggregation Neurodegenerative diseases Clinical diagnosis Alzheimer's disease Positron emission tomography (PET) tracer Tau |
| url | http://www.sciencedirect.com/science/article/pii/S2667325822004228 |
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