Amyloid β oligomerization is induced by brain lipid rafts

2006 ◽  
Vol 99 (3) ◽  
pp. 878-889 ◽  
Author(s):  
Sang-Il Kim ◽  
Jae-Sung Yi ◽  
Young-Gyu Ko
Keyword(s):  
Lipid Rafts ◽  
Amyloid Β ◽  
Brain Lipid

scholarly journals Persistence of psychosine in brain lipid rafts is a limiting factor in the therapeutic recovery of a mouse model for Krabbe disease

2010 ◽  
Vol 89 (3) ◽  
pp. 352-364 ◽  
Author(s):  
A.B. White ◽  
F. Galbiati ◽  
M.I. Givogri ◽  
A. Lopez Rosas ◽  
X. Qiu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lipid Rafts ◽  
Krabbe Disease ◽  
Limiting Factor ◽  
Brain Lipid

scholarly journals Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12181
Author(s):  
Guido Santos ◽  
Mario Díaz
Keyword(s):  
Alzheimer’S Disease ◽  
Mathematical Model ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Lipid Rafts ◽  
Brain Cortex ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Human Brain Cortex

Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology.

Amyloid-β Aggregation with Gold Nanoparticles on Brain Lipid Bilayer

Small ◽  
2014 ◽  
Vol 10 (9) ◽  
pp. 1779-1789 ◽  
Author(s):  
Hyojin Lee ◽  
Yuna Kim ◽  
Anna Park ◽  
Jwa-Min Nam
Keyword(s):  
Gold Nanoparticles ◽  
Lipid Bilayer ◽  
Amyloid Β ◽  
Brain Lipid

scholarly journals How Do the Size, Charge and Shape of Nanoparticles Affect Amyloid β Aggregation on Brain Lipid Bilayer?

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuna Kim ◽  
Ji-Hyun Park ◽  
Hyojin Lee ◽  
Jwa-Min Nam
Keyword(s):  
Lipid Bilayer ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Random Coil ◽  
Brain Lipid ◽  
Nanoparticle Shape ◽  
Total Brain ◽  
Aβ Aggregation ◽  
Shape Of Nanoparticles ◽  
The Brain

Abstract Here, we studied the effect of the size, shape and surface charge of Au nanoparticles (AuNPs) on amyloid beta (Aβ) aggregation on a total brain lipid-based supported lipid bilayer (brain SLB), a fluid platform that facilitates Aβ-AuNP aggregation process. We found that larger AuNPs induce large and amorphous aggregates on the brain SLB, whereas smaller AuNPs induce protofibrillar Aβ structures. Positively charged AuNPs were more strongly attracted to Aβ than negatively charged AuNPs and the stronger interactions between AuNPs and Aβ resulted in fewer β-sheets and more random coil structures. We also compared spherical AuNPs, gold nanorods (AuNRs) and gold nanocubes (AuNCs) to study the effect of nanoparticle shape on Aβ aggregation on the brain SLB. Aβ was preferentially bound to the long axis of AuNRs and fewer fibrils were formed whereas all the facets of AuNCs interacted with Aβ to produce the fibril networks. Finally, it was revealed that different nanostructures induce different cytotoxicity on neuroblastoma cells, and, overall, smaller Aβ aggregates induce higher cytotoxicity. The results offer insight into the roles of NPs and brain SLB in Aβ aggregation on the cell membrane and can facilitate the understanding of Aβ-nanostructure co-aggregation mechanism and tuning Aβ aggregate structures.

scholarly journals Amyloidogenic Processing of APP in Lipid Rafts

2010 ◽  
Vol 3 (1) ◽  
pp. 21-31
Author(s):  
Madepalli K. Lakshmana ◽  
Subhojit Roy ◽  
Kaihong Mi ◽  
David E. Kang
Keyword(s):  
Lipid Rafts ◽  
Lipid Raft ◽  
Amyloid Β ◽  
Convincing Evidence ◽  
Amyloid Β Peptide ◽  
Cholesterol Levels ◽  
Amyloidogenic Processing ◽  
Secretase Inhibitor ◽  
Aβ Generation ◽  
Lipid Raft Microdomains

Increased generation of amyloid β peptide (Aβ) derived from amyloid precursor protein (APP) is the primary pathological characteristic of Alzheimer’s disease (AD). However, the sub cellular compartment in which APP undergoes cleavage by secretases to generate Aβ is not precisely known. Compelling evidences suggest that amyloidogenic processing of APP occurs in lipid rafts. An indirect support for lipid raft processing of APP includes the localization of Aβ, APP C-terminal fragments (CTFs), APP holoprotein and secretases in the lipid raft microdomains, although few studies failed to find APP in the lipid rafts. The indirect support also comes from both experimental and clinical studies involving modulation of cholesterol levels and its effect on Aβ generation. Moderate depletion of cholesterol results in significant reduction in Aβ levels and increased dietary intake of cholesterol leads to higher levels of Aβ production suggesting that amyloidogenic processing of APP strongly depends on cholesterol levels and therefore on lipid raft integrity. More convincing evidence that lipid rafts are critical for amyloidogenic processing of APP comes from studies using antibody-mediated co-patching of APP and BACE1 which results in lipid raft association of APP and BACE1 and increased Aβ generation. Further, an endosome/lipid raft targeting of β-secretase inhibitor by sterol-mediated anchoring leading to reduced Aβ generation also suggests that lipid rafts are pivotal for amyloidogenic processing of APP. In the absence of an effective therapy for AD, proteins responsible for delivery of APP to lipid rafts including LRP, RanBP9 and ApoER2 may be excellent therapeutic targets in AD.

Amyloid-β Interactions with Lipid Rafts in Biomimetic Systems: A Review of Laboratory Methods

2020 ◽  
pp. 47-86
Author(s):  
Galya Staneva ◽  
Chiho Watanabe ◽  
Nicolas Puff ◽  
Vesela Yordanova ◽  
Michel Seigneuret ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Amyloid Β ◽  
Laboratory Methods ◽  
Biomimetic Systems

scholarly journals Prion Protein-mediated Toxicity of Amyloid-β Oligomers Requires Lipid Rafts and the Transmembrane LRP1

2013 ◽  
Vol 288 (13) ◽  
pp. 8935-8951 ◽  
Author(s):  
Jo V. Rushworth ◽  
Heledd H. Griffiths ◽  
Nicole T. Watt ◽  
Nigel M. Hooper
Keyword(s):  
Lipid Rafts ◽  
Prion Protein ◽  
Amyloid Β
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