Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development
Alzheimer’s disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (<i>Aβ</i>) triggers the disease. <i>Aβ</i> accumulates at the po...
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MDPI AG
2021-05-01
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| author | Anatoly S. Urban Konstantin V. Pavlov Anna V. Kamynina Ivan S. Okhrimenko Alexander S. Arseniev Eduard V. Bocharov |
| author_facet | Anatoly S. Urban Konstantin V. Pavlov Anna V. Kamynina Ivan S. Okhrimenko Alexander S. Arseniev Eduard V. Bocharov |
| author_sort | Anatoly S. Urban |
| collection | DOAJ |
| description | Alzheimer’s disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (<i>Aβ</i>) triggers the disease. <i>Aβ</i> accumulates at the points of contact of neurons in ordered cords and fibrils, forming the so-called senile plaques. <i>Aβ</i> isoforms of different lengths are found in healthy human brains regardless of age and appear to play a role in signaling pathways in the brain and to have neuroprotective properties at low concentrations. In recent years, different substances have been developed targeting <i>Aβ</i> production, aggregation, interaction with other molecules, and clearance, including peptide-based drugs. <i>Aβ</i> is a product of sequential cleavage of the membrane glycoprotein APP (amyloid precursor protein) by β- and γ-secretases. A number of familial mutations causing an early onset of the disease have been identified in the APP, especially in its transmembrane domain. The mutations are reported to influence the production, oligomerization, and conformational behavior of <i>Aβ</i> peptides. This review highlights the results of structural studies of the main proteins involved in Alzheimer’s disease pathogenesis and the molecular mechanisms by which perspective therapeutic substances can affect <i>Aβ</i> production and nucleation. |
| first_indexed | 2024-03-10T11:26:43Z |
| format | Article |
| id | doaj.art-467b0090289a49c7a051faa36381a146 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:26:43Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-467b0090289a49c7a051faa36381a1462023-11-21T19:36:13ZengMDPI AGMolecules1420-30492021-05-012610289710.3390/molecules26102897Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease DevelopmentAnatoly S. Urban0Konstantin V. Pavlov1Anna V. Kamynina2Ivan S. Okhrimenko3Alexander S. Arseniev4Eduard V. Bocharov5Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, RussiaFederal Clinical Center of Physical-Chemical Medicine of FMBA, 119435 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, RussiaAlzheimer’s disease is the most common type of neurodegenerative disease in the world. Genetic evidence strongly suggests that aberrant generation, aggregation, and/or clearance of neurotoxic amyloid-β peptides (<i>Aβ</i>) triggers the disease. <i>Aβ</i> accumulates at the points of contact of neurons in ordered cords and fibrils, forming the so-called senile plaques. <i>Aβ</i> isoforms of different lengths are found in healthy human brains regardless of age and appear to play a role in signaling pathways in the brain and to have neuroprotective properties at low concentrations. In recent years, different substances have been developed targeting <i>Aβ</i> production, aggregation, interaction with other molecules, and clearance, including peptide-based drugs. <i>Aβ</i> is a product of sequential cleavage of the membrane glycoprotein APP (amyloid precursor protein) by β- and γ-secretases. A number of familial mutations causing an early onset of the disease have been identified in the APP, especially in its transmembrane domain. The mutations are reported to influence the production, oligomerization, and conformational behavior of <i>Aβ</i> peptides. This review highlights the results of structural studies of the main proteins involved in Alzheimer’s disease pathogenesis and the molecular mechanisms by which perspective therapeutic substances can affect <i>Aβ</i> production and nucleation.https://www.mdpi.com/1420-3049/26/10/2897Alzheimer’s diseaseamyloid precursor proteinamyloid-β peptidestructural–dynamical propertiestoxic oligomerizationmolecular mechanism |
| spellingShingle | Anatoly S. Urban Konstantin V. Pavlov Anna V. Kamynina Ivan S. Okhrimenko Alexander S. Arseniev Eduard V. Bocharov Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development Molecules Alzheimer’s disease amyloid precursor protein amyloid-β peptide structural–dynamical properties toxic oligomerization molecular mechanism |
| title | Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development |
| title_full | Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development |
| title_fullStr | Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development |
| title_full_unstemmed | Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development |
| title_short | Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer’s Disease Development |
| title_sort | structural studies providing insights into production and conformational behavior of amyloid β peptide associated with alzheimer s disease development |
| topic | Alzheimer’s disease amyloid precursor protein amyloid-β peptide structural–dynamical properties toxic oligomerization molecular mechanism |
| url | https://www.mdpi.com/1420-3049/26/10/2897 |
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