Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms
Most therapeutic agents are designed to target a molecule or pathway without consideration of the mechanisms involved in the physiological turnover or removal of that target. In light of this and in particular for Alzheimer’s disease, a number of therapeutic interventions are presently being develo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-05-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00064/full |
| _version_ | 1828433612904595456 |
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| author | Christopher eMorrone Mingzhe eLiu Sandra E Black Joanne eMclaurin |
| author_facet | Christopher eMorrone Mingzhe eLiu Sandra E Black Joanne eMclaurin |
| author_sort | Christopher eMorrone |
| collection | DOAJ |
| description | Most therapeutic agents are designed to target a molecule or pathway without consideration of the mechanisms involved in the physiological turnover or removal of that target. In light of this and in particular for Alzheimer’s disease, a number of therapeutic interventions are presently being developed/investigated which target the amyloid-β peptide (Aβ). However, the literature has not adequately considered which Aβ physiological clearance pathways are necessary and sufficient for the effective action of these therapeutics. In this review, we evaluate the therapeutic strategies targeting Aβ presently in clinical development, discuss the possible interaction of these treatments with pathways that under normal physiological conditions are responsible for the turnover of Aβ and highlight possible caveats. We consider immunization strategies primarily reliant on a peripheral sink mechanism of action, small molecules that are reliant on entry into the CNS and thus degradation pathways within the brain as well as lifestyle interventions that affect vascular, parenchymal and peripheral degradation pathways. We propose that effective development of Alzheimer’s disease therapeutic strategies targeting Aβ peptide will require consideration of the age- and disease-specific changes to endogenous Aβ clearance mechanisms in order to elicit maximal efficacy. |
| first_indexed | 2024-12-10T18:38:01Z |
| format | Article |
| id | doaj.art-2b1de6591f694e1b8378a9eea8ccc0bb |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-10T18:38:01Z |
| publishDate | 2015-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-2b1de6591f694e1b8378a9eea8ccc0bb2022-12-22T01:37:44ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652015-05-01710.3389/fnagi.2015.00064135545Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanismsChristopher eMorrone0Mingzhe eLiu1Sandra E Black2Joanne eMclaurin3Sunnybrook Research InstituteSunnybrook Research InstituteSunnybrook Research InstituteSunnybrook Research InstituteMost therapeutic agents are designed to target a molecule or pathway without consideration of the mechanisms involved in the physiological turnover or removal of that target. In light of this and in particular for Alzheimer’s disease, a number of therapeutic interventions are presently being developed/investigated which target the amyloid-β peptide (Aβ). However, the literature has not adequately considered which Aβ physiological clearance pathways are necessary and sufficient for the effective action of these therapeutics. In this review, we evaluate the therapeutic strategies targeting Aβ presently in clinical development, discuss the possible interaction of these treatments with pathways that under normal physiological conditions are responsible for the turnover of Aβ and highlight possible caveats. We consider immunization strategies primarily reliant on a peripheral sink mechanism of action, small molecules that are reliant on entry into the CNS and thus degradation pathways within the brain as well as lifestyle interventions that affect vascular, parenchymal and peripheral degradation pathways. We propose that effective development of Alzheimer’s disease therapeutic strategies targeting Aβ peptide will require consideration of the age- and disease-specific changes to endogenous Aβ clearance mechanisms in order to elicit maximal efficacy.http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00064/fullTherapeuticsVaccineAlzheimer’s diseaselifestyle factorsClearanceAmyloid-β peptide |
| spellingShingle | Christopher eMorrone Mingzhe eLiu Sandra E Black Joanne eMclaurin Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms Frontiers in Aging Neuroscience Therapeutics Vaccine Alzheimer’s disease lifestyle factors Clearance Amyloid-β peptide |
| title | Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms |
| title_full | Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms |
| title_fullStr | Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms |
| title_full_unstemmed | Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms |
| title_short | Interaction between therapeutic interventions for Alzheimer’s disease and physiological Aβ clearance mechanisms |
| title_sort | interaction between therapeutic interventions for alzheimer s disease and physiological aβ clearance mechanisms |
| topic | Therapeutics Vaccine Alzheimer’s disease lifestyle factors Clearance Amyloid-β peptide |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00064/full |
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