Τίτλος:
Clusterin in Alzheimer's disease: An amyloidogenic inhibitor of amyloid formation?
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Clusterin is a heterodimeric glycoprotein (α- and β-chain), which has been described as an extracellular molecular chaperone. In humans, clusterin is an amyloid-associated protein, co-localizing with fibrillar deposits in several amyloidoses, including Alzheimer's disease. To clarify its potential implication in amyloid formation, we located aggregation-prone regions within the sequence of clusterin α-chain, via computational methods. We had peptide-analogues, which correspond to each of these regions, chemically synthesized and experimentally demonstrated that all of them can form amyloid-like fibrils. We also provide evidence that the same peptide-analogues can inhibit amyloid-β fibril formation, potentially making them appropriate drug candidates for Alzheimer's disease. At the same time, our findings hint that the respective aggregation-prone clusterin regions may be implicated in the molecular mechanism in which clusterin inhibits amyloid formation. Furthermore, we suggest that molecular chaperones with amyloidogenic properties might have a role in the regulation of amyloid formation, essentially acting as functional amyloids. © 2022
Συγγραφείς:
Spatharas, P.M.
Nasi, G.I.
Tsiolaki, P.L.
Theodoropoulou, M.K.
Papandreou, N.C.
Hoenger, A.
Trougakos, I.P.
Iconomidou, V.A.
Περιοδικό:
Biochimica et Biophysica Acta. Molecular Basis of Disease
Λέξεις-κλειδιά:
amyloid; clusterin; glycoprotein, Alzheimer disease; amyloidosis; chemistry; human; metabolism, Alzheimer Disease; Amyloid; Amyloidosis; Clusterin; Glycoproteins; Humans
DOI:
10.1016/j.bbadis.2022.166384
