A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease
AbstractCholinesterase (ChE) enzymes have been identified as diagnostic markers for Alzheimer disease (AD). Substrate-based probes have been synthesised to detect ChEs but they have not detected changes in ChE distribution associated with AD pathology. Probes are typically screened using spectrophot...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2225797 |
| _version_ | 1797400973026525184 |
|---|---|
| author | Sultan Darvesh Scott Banfield Maeve Dufour Katrina L. Forrestall Hillary Maillet G. Andrew Reid Dane Sands Ian R. Pottie |
| author_facet | Sultan Darvesh Scott Banfield Maeve Dufour Katrina L. Forrestall Hillary Maillet G. Andrew Reid Dane Sands Ian R. Pottie |
| author_sort | Sultan Darvesh |
| collection | DOAJ |
| description | AbstractCholinesterase (ChE) enzymes have been identified as diagnostic markers for Alzheimer disease (AD). Substrate-based probes have been synthesised to detect ChEs but they have not detected changes in ChE distribution associated with AD pathology. Probes are typically screened using spectrophotometric methods with pure enzyme for specificity and kinetics. However, the biochemical properties of ChEs associated with AD pathology are altered. The present work was undertaken to determine whether the Karnovsky-Roots (KR) histochemical method could be used to evaluate probes at the site of pathology. Thirty thioesters and esters were synthesised and evaluated using enzyme kinetic and KR methods. Spectrophotometric methods demonstrated all thioesters were ChE substrates, yet only a few provided staining in the brain with the KR method. Esters were ChE substrates with interactions with brain ChEs. These results suggest that the KR method may provide an efficient means to screen compounds as probes for imaging AD-associated ChEs. |
| first_indexed | 2024-03-09T02:03:11Z |
| format | Article |
| id | doaj.art-c958e74950c54e83ac55b4fa6fec5a01 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:03:11Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c958e74950c54e83ac55b4fa6fec5a012023-12-08T03:24:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2225797A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s diseaseSultan Darvesh0Scott Banfield1Maeve Dufour2Katrina L. Forrestall3Hillary Maillet4G. Andrew Reid5Dane Sands6Ian R. Pottie7Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Chemistry and Physics, Mount St. Vincent University, Halifax, Nova Scotia, CanadaAbstractCholinesterase (ChE) enzymes have been identified as diagnostic markers for Alzheimer disease (AD). Substrate-based probes have been synthesised to detect ChEs but they have not detected changes in ChE distribution associated with AD pathology. Probes are typically screened using spectrophotometric methods with pure enzyme for specificity and kinetics. However, the biochemical properties of ChEs associated with AD pathology are altered. The present work was undertaken to determine whether the Karnovsky-Roots (KR) histochemical method could be used to evaluate probes at the site of pathology. Thirty thioesters and esters were synthesised and evaluated using enzyme kinetic and KR methods. Spectrophotometric methods demonstrated all thioesters were ChE substrates, yet only a few provided staining in the brain with the KR method. Esters were ChE substrates with interactions with brain ChEs. These results suggest that the KR method may provide an efficient means to screen compounds as probes for imaging AD-associated ChEs.https://www.tandfonline.com/doi/10.1080/14756366.2023.2225797ButyrylcholinesteraseacetylcholinesteraseAlzheimer’s diseaseneuroimagingradioligands |
| spellingShingle | Sultan Darvesh Scott Banfield Maeve Dufour Katrina L. Forrestall Hillary Maillet G. Andrew Reid Dane Sands Ian R. Pottie A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease Journal of Enzyme Inhibition and Medicinal Chemistry Butyrylcholinesterase acetylcholinesterase Alzheimer’s disease neuroimaging radioligands |
| title | A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease |
| title_full | A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease |
| title_fullStr | A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease |
| title_full_unstemmed | A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease |
| title_short | A method for the efficient evaluation of substrate-based cholinesterase imaging probes for Alzheimer’s disease |
| title_sort | method for the efficient evaluation of substrate based cholinesterase imaging probes for alzheimer s disease |
| topic | Butyrylcholinesterase acetylcholinesterase Alzheimer’s disease neuroimaging radioligands |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2225797 |
| work_keys_str_mv | AT sultandarvesh amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT scottbanfield amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT maevedufour amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT katrinalforrestall amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT hillarymaillet amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT gandrewreid amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT danesands amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT ianrpottie amethodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT sultandarvesh methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT scottbanfield methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT maevedufour methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT katrinalforrestall methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT hillarymaillet methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT gandrewreid methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT danesands methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease AT ianrpottie methodfortheefficientevaluationofsubstratebasedcholinesteraseimagingprobesforalzheimersdisease |