Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges
To completely treat and ultimately prevent dementia, it is essential to elucidate its pathogenic mechanisms in detail. There are two major hypotheses for the pathogenesis of Alzheimer’s dementia: the β-amyloid (Aβ) hypothesis and the tau hypothesis. The modified amyloid hypothesis, which proposes th...
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| Format: | Article |
| Language: | English |
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The Biophysical Society of Japan
2023-03-01
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| Series: | Biophysics and Physicobiology |
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| Online Access: | https://doi.org/10.2142/biophysico.bppb-v20.0007 |
| _version_ | 1811155157156626432 |
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| author | Hidekazu Hiroaki |
| author_facet | Hidekazu Hiroaki |
| author_sort | Hidekazu Hiroaki |
| collection | DOAJ |
| description | To completely treat and ultimately prevent dementia, it is essential to elucidate its pathogenic mechanisms in detail. There are two major hypotheses for the pathogenesis of Alzheimer’s dementia: the β-amyloid (Aβ) hypothesis and the tau hypothesis. The modified amyloid hypothesis, which proposes that toxic oligomers rather than amyloid fibrils are the essential cause, has recently emerged. Aβ peptides [Aβ(1–40) and Aβ(1–42)] form highly insoluble aggregates in vivo and in vitro. These Aβ aggregates contain many polymorphisms, whereas Aβ peptides are intrinsically disordered in physiological aqueous solutions without any compact conformers. Over the last three decades, solid-state nuclear magnetic resonance (NMR) has greatly contributed to elucidating the structure of each polymorph, while solution NMR has revealed the dynamic nature of the transient conformations of the monomer. Moreover, several methods to investigate the aggregation process based on the observation of magnetization saturation transfer have also been developed. The complementary use of NMR methods with cryo-electron microscopy, which has rapidly matured, is expected to clarify the relationship between the amyloid and molecular pathology of Alzheimer’s dementia in the near future. This review article is an extended version of the Japanese article, Insights into the Mechanisms of Oligomerization/Fibrilization of Amyloid β Peptide from Nuclear Magnetic Resonance, published in SEIBUTSU BUTSURI Vol. 62, p. 39–42 (2022). |
| first_indexed | 2024-04-10T04:28:27Z |
| format | Article |
| id | doaj.art-54c6feffc52241938cd8670f78ee23b4 |
| institution | Directory Open Access Journal |
| issn | 2189-4779 |
| language | English |
| last_indexed | 2024-04-10T04:28:27Z |
| publishDate | 2023-03-01 |
| publisher | The Biophysical Society of Japan |
| record_format | Article |
| series | Biophysics and Physicobiology |
| spelling | doaj.art-54c6feffc52241938cd8670f78ee23b42023-03-10T08:23:46ZengThe Biophysical Society of JapanBiophysics and Physicobiology2189-47792023-03-012010.2142/biophysico.bppb-v20.0007Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challengesHidekazu Hiroaki0Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Aichi 464-8601, JapanTo completely treat and ultimately prevent dementia, it is essential to elucidate its pathogenic mechanisms in detail. There are two major hypotheses for the pathogenesis of Alzheimer’s dementia: the β-amyloid (Aβ) hypothesis and the tau hypothesis. The modified amyloid hypothesis, which proposes that toxic oligomers rather than amyloid fibrils are the essential cause, has recently emerged. Aβ peptides [Aβ(1–40) and Aβ(1–42)] form highly insoluble aggregates in vivo and in vitro. These Aβ aggregates contain many polymorphisms, whereas Aβ peptides are intrinsically disordered in physiological aqueous solutions without any compact conformers. Over the last three decades, solid-state nuclear magnetic resonance (NMR) has greatly contributed to elucidating the structure of each polymorph, while solution NMR has revealed the dynamic nature of the transient conformations of the monomer. Moreover, several methods to investigate the aggregation process based on the observation of magnetization saturation transfer have also been developed. The complementary use of NMR methods with cryo-electron microscopy, which has rapidly matured, is expected to clarify the relationship between the amyloid and molecular pathology of Alzheimer’s dementia in the near future. This review article is an extended version of the Japanese article, Insights into the Mechanisms of Oligomerization/Fibrilization of Amyloid β Peptide from Nuclear Magnetic Resonance, published in SEIBUTSU BUTSURI Vol. 62, p. 39–42 (2022).https://doi.org/10.2142/biophysico.bppb-v20.0007solid state nmrsolution nmrbeta-amyloid hypothesistoxic aβ oligomernucleation-dependent polymerization |
| spellingShingle | Hidekazu Hiroaki Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges Biophysics and Physicobiology solid state nmr solution nmr beta-amyloid hypothesis toxic aβ oligomer nucleation-dependent polymerization |
| title | Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges |
| title_full | Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges |
| title_fullStr | Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges |
| title_full_unstemmed | Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges |
| title_short | Molecular mechanisms of amyloid-β peptide fibril and oligomer formation: NMR-based challenges |
| title_sort | molecular mechanisms of amyloid β peptide fibril and oligomer formation nmr based challenges |
| topic | solid state nmr solution nmr beta-amyloid hypothesis toxic aβ oligomer nucleation-dependent polymerization |
| url | https://doi.org/10.2142/biophysico.bppb-v20.0007 |
| work_keys_str_mv | AT hidekazuhiroaki molecularmechanismsofamyloidbpeptidefibrilandoligomerformationnmrbasedchallenges |