Three-dimensional and fractal analyses of assemblies of amyloid β protein subtypes [Aβ40 and Aβ42(43)] in canine senile plaques

2001 ◽  
Vol 103 (3) ◽  
pp. 228-236 ◽  
Author(s):  
Kyoko Miyawaki ◽  
Hiroyuki Nakayama ◽  
Sayoko Matsuno ◽  
Akira Tamaoka ◽  
Kunio Doi
2019 ◽  
Vol 29 (3) ◽  
pp. 382-393 ◽  
Author(s):  
Saori Hata ◽  
Anqi Hu ◽  
Yi Piao ◽  
Tadashi Nakaya ◽  
Hidenori Taru ◽  
...  

Abstract A neuropathologic hallmark of Alzheimer’s disease (AD) is the presence of senile plaques that contain neurotoxic amyloid-β protein (Aβ) species, which are generated by the cleavage of amyloid β-protein precursor by secretases such as the γ-secretase complex, preferentially located in detergent-resistant membrane (DRM) regions and comprising endoproteolysed amino- and carboxy-terminal fragments of presenilin, nicastrin, anterior pharynx defective 1 and presenilin enhancer 2. Whereas some of familial AD patients harbor causative PSEN mutations that lead to more generation of neurotoxic Aβ42, the contribution of Aβ generation to sporadic/late-onset AD remains unclear. We found that the carboxy-terminal fragment of presenilin 1 was redistributed from DRM regions to detergent-soluble membrane (non-DRM) regions in brain tissue samples from individuals with sporadic AD. DRM fractions from AD brain sample had the ability to generate significantly more Aβ and had a lower cholesterol content than DRM fractions from non-demented control subjects. We further demonstrated that lowering the cholesterol content of DRM regions from cultured cells contributed to the redistribution of γ-secretase components and Aβ production. Taken together, the present analyses suggest that the lowered cholesterol content in DRM regions may be a cause of sporadic/late-onset AD by enhancing overall Aβ generation.


Science ◽  
2017 ◽  
Vol 358 (6359) ◽  
pp. 116-119 ◽  
Author(s):  
Lothar Gremer ◽  
Daniel Schölzel ◽  
Carla Schenk ◽  
Elke Reinartz ◽  
Jörg Labahn ◽  
...  

Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer’s disease patients. We present the structure of an Aβ(1–42) fibril composed of two intertwined protofilaments determined by cryo–electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall “LS”-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed “groove” and “ridge,” leading to different binding pathways on both fibril ends, which has implications for fibril growth.


1997 ◽  
Vol 94 (4) ◽  
pp. 323-328 ◽  
Author(s):  
Shin'ichiro Nakamura ◽  
Akira Tamaoka ◽  
Naoya Sawamura ◽  
Wijit Kiatipattanasakul ◽  
Hiroyuki Nakayama ◽  
...  

2000 ◽  
Vol 162 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Ichiro Isobe ◽  
Katsuhiko Yanagisawa ◽  
Makoto Michikawa

2021 ◽  
pp. 1-21
Author(s):  
Xi-Jun Song ◽  
He-Yan Zhou ◽  
Yu-Ying Sun ◽  
Han-Chang Huang

Alzheimer’s disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-β (Aβ) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-β protein precursor (AβPP) through the successive cleaving by β-site AβPP-cleavage enzyme 1 (BACE1) and γ-secretase. AβPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AβPP. In the recent years, about 10 phosphorylation sites of AβPP were identified, and they play complex roles in glycosylation modification and cleavage of AβPP. In this article, we introduced the transport and the cleavage pathways of AβPP, then summarized the phosphorylation and glycosylation sites of AβPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AβPP trafficking and cleavage in order to provide theoretical basis for AD research.


2018 ◽  
Vol 15 (14) ◽  
pp. 1283-1296 ◽  
Author(s):  
Tadanori Hamano ◽  
Kouji Hayashi ◽  
Norimichi Shirafuji ◽  
Yasunari Nakamoto

The pathogenic mechanisms of Alzheimer’s Disease (AD) involve the deposition of abnormally misfolded proteins, amyloid β protein (Aβ) and tau protein. Aβ comprises senile plaques, and tau aggregates form Neurofibrillary Tangles (NFTs), both of which are hallmarks of AD. Autophagy is the main conserved pathway for the degeneration of aggregated proteins, Aβ, tau and dysfunctional organelles in the cell. Many animal model studies have demonstrated that autophagy normally functions as the protective factor against AD progression associated with intracytoplasmic toxic Aβ and tau aggregates. The upregulation of autophagy can also be favorable in AD treatment. An improved understanding of the signaling pathways that regulate autophagy is critical to developing AD treatments. The cellular and molecular machineries of autophagy, their function in the pathogenesis of AD, and current drug discovery strategies will be discussed in this review.


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