Amyloid fibril formation

Amyloid deposits are complex structures where the amyloid fibrils are intertwined with several other amyloid proteins that are always present in the deposits, regardless of the type of amyloid fibril. Highly sulfated proteoglycans (e.g. heparan sulfate proteoglycan, or HSPG), which are integral structural components of cellular basement membranes, are common constituents of amyloid deposits in all known types of amyloidosis thus far investigated.

These common elements are thought to play an active role in the initiation of amyloid fibril formation and deposition, and consequently, amyloid-related disorders. These proteoglycans, more specifically the sulfated glycosaminoglycan (GAG) molecule portion of specific proteoglycans, have been shown to interact with the amyloidogenic amyloid proteins. By doing so, these GAGs promote fibril formation.

GAGs bind to the amyloid proteins

The "Amyloid Cascade"

Amyloid production and decreased cell clearance of the amyloid result in a cascade of events that eventually leads to cellular dysfunction, cell death and associated conditions such as AA Amyloidosis, Alzheimer's disease and hemorrhagic stroke due to cerebral amyloid angiopathy. When more and more binding occurs, the fibrils can lead to higher cell death levels, and early disruption of an organ's overall function.

By binding to the proteins, GAGs promote a structural shift of the
amyloid proteins, which become fibrillar.
The GAG associated fibrils deposit around cells in affected organs.

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