Amyloid β
2022-02-08 links: reference:
Amyloid β #
- Not only found in Alzheimer’s, but many other neurodegenerative diseases:
- But perhaps not: Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease
- Brain Accumulation of Amyloid-beta in Non-Alzheimer Neurodegeneration. Amyloid-beta accumulation is frequently seen in Alzheimer’s, Pick’s, Parkinson’s, and multiple systems atrophy, but not in ALS.
- Itself the component of amyloid plaques, which are associated with an abundance of microglia but also astrocytes. Basically they misfold, and this misfolding spreads to other oligomers.
- Absence of Aβ does not lead to any obvious loss of physiological function. Activates kinase enzymes, protects against oxidative stress, regulates cholesterol transport, anti-microbial. Indeed there’s quite a lot of evidence it’s a response and not causative in disease.
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An iron-export ferroxidase activity of β-amyloid protein precursor is inhibited by zinc in Alzheimer’s Disease
- APP catalytically oxidizes Fe2+, loads Fe3+ into transferrin, and has a major interaction with ferroportin in HEK293T cells (that lack ceruloplasmin) and in human cortical tissue.-
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The amyloid beta peptide: a chemist’s perspective. Role in Alzheimer’s and fibrillization
- Denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer’s disease??
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Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death
- Amyloid beta-peptide is central to the pathogenesis of Alzheimer’s?
- Abeta induces Lipid Peroxidation in ways that are inhibited by antioxidants.
- Creatine Kinase (inhibited by Aβ) and beta-actin have increased carbonyl groups, and GLT-1, has increased binding of HNE in AD.
- Synaptosomes from Apolipoprotein E knock-out mice are more vulnerable to Abeta-induced oxidative stress (protein oxidation, lipid peroxidation, and ROS generation)
- Increases presynaptic and astrocytic Glutamate release, and inhibits Glutamate Transporter activity+expression via activating (phosphorylating) the MAPKs.
- This can almost double the amount of time to clear synaptically released glutamate.
- Increases astrocytic calcium via binding to α7 nAChR (with high affinity apparently).
- Increases NADPH Oxidase
- Its formation might be described as a consequence of low brain sulfate groups:
Lipid Rafts #
- Degredation is dependent on astrocytic Apolipoprotein E.