Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment
Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/5091 |
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| author | Haruki Koike Yohei Iguchi Kentaro Sahashi Masahisa Katsuno |
| author_facet | Haruki Koike Yohei Iguchi Kentaro Sahashi Masahisa Katsuno |
| author_sort | Haruki Koike |
| collection | DOAJ |
| description | Amyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrated the appearance of small globular oligomeric species during the incubation of amyloid beta peptide (Aβ). Nerve biopsy specimens from patients with systemic amyloidosis have suggested that globular structures similar to Aβ oligomers were generated from amorphous electron-dense materials and later developed into mature amyloid fibrils. Schwann cells adjacent to amyloid fibrils become atrophic and degenerative, suggesting that the direct tissue damage induced by amyloid fibrils plays an important role in systemic amyloidosis. In contrast, there is increasing evidence that oligomers, rather than amyloid fibrils, are responsible for cell death in neurodegenerative diseases, particularly Alzheimer’s disease. Disease-modifying therapies based on the pathophysiology of amyloidosis have now become available. Aducanumab, a human monoclonal antibody against the aggregated form of Aβ, was recently approved for Alzheimer’s disease, and other monoclonal antibodies, including gantenerumab, solanezumab, and lecanemab, could also be up for approval. As many other agents for amyloidosis will be developed in the future, studies to develop sensitive clinical scales for identifying improvement and markers that can act as surrogates for clinical scales should be conducted. |
| first_indexed | 2024-03-10T08:31:57Z |
| format | Article |
| id | doaj.art-2aa82b95237c4529a1a22217e8ba41a9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:31:57Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-2aa82b95237c4529a1a22217e8ba41a92023-11-22T08:56:31ZengMDPI AGMolecules1420-30492021-08-012616509110.3390/molecules26165091Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and TreatmentHaruki Koike0Yohei Iguchi1Kentaro Sahashi2Masahisa Katsuno3Department of Neurology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Neurology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Neurology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanDepartment of Neurology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, JapanAmyloidosis is a term referring to a group of various protein-misfolding diseases wherein normally soluble proteins form aggregates as insoluble amyloid fibrils. How, or whether, amyloid fibrils contribute to tissue damage in amyloidosis has been the topic of debate. In vitro studies have demonstrated the appearance of small globular oligomeric species during the incubation of amyloid beta peptide (Aβ). Nerve biopsy specimens from patients with systemic amyloidosis have suggested that globular structures similar to Aβ oligomers were generated from amorphous electron-dense materials and later developed into mature amyloid fibrils. Schwann cells adjacent to amyloid fibrils become atrophic and degenerative, suggesting that the direct tissue damage induced by amyloid fibrils plays an important role in systemic amyloidosis. In contrast, there is increasing evidence that oligomers, rather than amyloid fibrils, are responsible for cell death in neurodegenerative diseases, particularly Alzheimer’s disease. Disease-modifying therapies based on the pathophysiology of amyloidosis have now become available. Aducanumab, a human monoclonal antibody against the aggregated form of Aβ, was recently approved for Alzheimer’s disease, and other monoclonal antibodies, including gantenerumab, solanezumab, and lecanemab, could also be up for approval. As many other agents for amyloidosis will be developed in the future, studies to develop sensitive clinical scales for identifying improvement and markers that can act as surrogates for clinical scales should be conducted.https://www.mdpi.com/1420-3049/26/16/5091AA amyloidosisAL amyloidosisAlzheimer’s diseaseamyotrophic lateral sclerosisATTR amyloidosisdementia |
| spellingShingle | Haruki Koike Yohei Iguchi Kentaro Sahashi Masahisa Katsuno Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment Molecules AA amyloidosis AL amyloidosis Alzheimer’s disease amyotrophic lateral sclerosis ATTR amyloidosis dementia |
| title | Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment |
| title_full | Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment |
| title_fullStr | Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment |
| title_full_unstemmed | Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment |
| title_short | Significance of Oligomeric and Fibrillar Species in Amyloidosis: Insights into Pathophysiology and Treatment |
| title_sort | significance of oligomeric and fibrillar species in amyloidosis insights into pathophysiology and treatment |
| topic | AA amyloidosis AL amyloidosis Alzheimer’s disease amyotrophic lateral sclerosis ATTR amyloidosis dementia |
| url | https://www.mdpi.com/1420-3049/26/16/5091 |
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