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Published online by Cambridge University Press: 02 July 2020
Proteasomes are multicatalytic structures found in cells that play a major role in the proteolytic degradation of proteins. Before entering the proteasome, proteins are marked like trees to be cut by attachment of ubiquitin. Neurodegenerative disorders of aging, including Alzheimer's, show abnormal accumulation of plaques and neurofibrillary tangles (NT). The latter are composed of paired helical filaments containing ubiquitinated tau protein. The fact that ubiquitinated tau is not degraded by the proteasomes may be a key to the formation of NT. Proteasomes, like other cellular pathways, are controlled by various mechanisms. It was found that amyloid β protein (Aβ) inhibits chymotrypsin-like proteasomal activity. Additionally, Aβ was found in elevated quantity in NTs in Alzheimer's diseased brain tissue. Understanding the mechanism of action of Aβ therefore becomes important.
In order to track the regulatory Aβ protein (Aβ1-40), a variant was synthesized with a terminal cysteine (Aβ1-40C40) that could be gold labeled.