University Biology Report: Formation of Amyloid Fibrils and Disease

This report explores the formation of amyloid fibrils, insoluble fibers formed from the aggregation of soluble proteins. It highlights the link between amyloid fibrils and various human diseases, with a focus on Alzheimer's disease. The report discusses the role of the amyloid precursor protein (APP) and the formation of beta-amyloid peptides in the brain tissue of Alzheimer's patients. It examines the Aβ hypothesis, membrane-mediated amyloidogenesis, and the interaction between beta-amyloid and monosialoganglioside GM1, particularly the role of GM1 clusters and cholesterol in facilitating aggregation. The report also covers the conversion of beta-sheets into a second beta-structure, the formation of toxic amyloid fibrils, and the cytotoxic effects of GM1 clusters. The research emphasizes the importance of understanding these processes to address neurodegenerative diseases.

FORMATION OF AMYLOIDS FIBRILS
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The amyloid fibrils are formed when the soluble proteins assemble leading to the formation of
insoluble fibers that are non-degradable. Formation of insoluble fibers can be accompanied by
many human diseases of where each disease is described by a particular protein that aggregates.
These abnormal proteins called amyloid causes amyloidosis. The gene APP gives instructions for
the production of the amyloid precursor protein. This amyloid protein is present in body organs
and tissue such as spinal cord and the brain. Under the vitro and vivo conditions, there is the
development of amyloid fibrils protein aggregates. The amyloid fibril protein that is found in the
brain tissue of a patient with Alzheimer are made from the beta-A peptide, and they are
associated with neurodegeneration (Kotler et al, 2014).
As per the the Aβ hypothesis during the explanation of the Alzheimer illness, the Aβ peptides of
39-43 amino acids remains aggregate and draw them into the neurons that ignites the neurotoxic
cascades of the infection (Abeln et al, 2014). The researches on the investigation on the amyloid
beta-peptide in the aqueous solution shown that the amyloid fibrils are less toxic as compared to
oligomer peptides apparatuses. This led to the researcher shifting their attention to the soluble
oligomers which were more toxic. The research mainly focused on the membrane-mediated
amyloidogenesis.
Earlier studies had shown that there are specific beta-amyloid that were connected to
monosialoganglioside GM, which is sugar lipid in the patient’s brains who had earlier showed
pathological changes that were associated with Alzheimer infection. Those researchers found
that beta-amyloid binds to specific GM1 which occur in clusters and not uniformly occurring.
Cholesterol facilitates clustering.

During binding, beta-amyloid alters its structure from a coil to a helix form. The interaction of
carbohydrates and the aromatic amino-group chain moieties to GM1 for binding process. The
beta-amyloid deposits and reaches its initial threshold concentration. The aggregate beta-sheets
of 15 molecules occur and exist in a helical form. As the disease progresses the beta-amyloid/
GM1 ration exceeds the threshold and the beta- structure is converted into the second beta-
structure that can seed aggregate (Chiti, and Dobson, 2017). The seed aggregates monomers
from the aqueous changes into the poisonous amyloid fibrils form that are hydrophobic and
contains antiparallel beta-sheets. The less polar toxicity of the GM1 bands is responsible for the
toxic fibrils formation. Membranes with GM1 clusters accelerate the aggregation of beta-
amyloid through concentration of the Aβ molecules and generate unique amyloid fibrils
structures which are significantly cytotoxic (Matsuzaki, 2014).

Reference
Abeln, S., Vendruscolo, M., Dobson, C.M. and Frenkel, D., 2014. A simple lattice model that
captures protein folding, aggregation and amyloid formation. PloS one, 9(1), p.e85185.
Chiti, F. and Dobson, C.M., 2017. Protein misfolding, amyloid formation, and human disease: a
summary of progress over the last decade. Annual review of biochemistry, 86, pp.27-68.
Kotler, S.A., Walsh, P., Brender, J.R. and Ramamoorthy, A., 2014. Differences between
amyloid-β aggregation in solution and on the membrane: insights into elucidation of the
mechanistic details of Alzheimer's disease. Chemical Society Reviews, 43(19), pp.6692-6700.
Matsuzaki, K., 2014. How do membranes initiate Alzheimer’s Disease? Formation of toxic
amyloid fibrils by the amyloid β-protein on ganglioside clusters. Accounts of chemical research,
47(8), pp.2397-2404.