The Ultrastructure of Tissue Damage by Amyloid Fibrils
Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure...
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doaj-a60e5a260d3849f9bb6501b5c438c21d2021-08-06T15:29:18ZengMDPI AGMolecules1420-30492021-07-01264611461110.3390/molecules26154611The Ultrastructure of Tissue Damage by Amyloid FibrilsHaruki Koike0Masahisa Katsuno1Department 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 group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: (1) reducing or preventing the production of causative proteins; (2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or (3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.https://www.mdpi.com/1420-3049/26/15/4611chemotherapydiflunisalelectron microscopyinotersenneurodegenerationpathogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haruki Koike Masahisa Katsuno |
spellingShingle |
Haruki Koike Masahisa Katsuno The Ultrastructure of Tissue Damage by Amyloid Fibrils Molecules chemotherapy diflunisal electron microscopy inotersen neurodegeneration pathogenesis |
author_facet |
Haruki Koike Masahisa Katsuno |
author_sort |
Haruki Koike |
title |
The Ultrastructure of Tissue Damage by Amyloid Fibrils |
title_short |
The Ultrastructure of Tissue Damage by Amyloid Fibrils |
title_full |
The Ultrastructure of Tissue Damage by Amyloid Fibrils |
title_fullStr |
The Ultrastructure of Tissue Damage by Amyloid Fibrils |
title_full_unstemmed |
The Ultrastructure of Tissue Damage by Amyloid Fibrils |
title_sort |
ultrastructure of tissue damage by amyloid fibrils |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-07-01 |
description |
Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: (1) reducing or preventing the production of causative proteins; (2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or (3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis. |
topic |
chemotherapy diflunisal electron microscopy inotersen neurodegeneration pathogenesis |
url |
https://www.mdpi.com/1420-3049/26/15/4611 |
work_keys_str_mv |
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