Amyloid-β Increases Activity of Proteasomes Capped with 19S and 11S Regulators

Article type: Research Article

Authors: Morozov, Alexey V.^a | Kulikova, Alexandra A.^a | Astakhova, Tatiana M.^b | Mitkevich, Vladimir A.^a | Burnysheva, Ksenia M.^a | Adzhubei, Alexei A.^a | Erokhov, Pavel A.^b | Evgen’ev, Michail B.^a | Sharova, Natalia P.^b | Karpov, Vadim L.^a | Makarov, Alexander A.^{a; *}

Affiliations: [a] Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia | [b] Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia

Correspondence: [*] Correspondence to: Alexander A. Makarov, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991, Moscow, Russia. Tel.: +7 499 1354095; Fax: +7 499 1351405; E-mail: aamakarov@eimb.ru.

Abstract: Accumulation of amyloid-β (Aβ) in neurons accompanies Alzheimer’s disease progression. In the cytoplasm Aβ influences activity of proteasomes, the multisubunit protein complexes that hydrolyze the majority of intracellular proteins. However, the manner in which Aβ affects the proteolytic activity of proteasomes has not been established. In this study the effect of Aβ42 and Aβ42 with isomerized Asp7 on activity of different forms of proteasomes has been analyzed. It has been shown that Aβ peptides efficiently reduce activity of the 20S proteasomes, but increase activity of the 20S proteasomes capped with the 19S and/or 11S regulators. Modulation of proteasome activity is mainly determined by the C-terminal segment of Aβ (amino acids 17-42). This study demonstrated an important role of proteasome regulators in the interplay between Aβ and the proteasomes.

Keywords: Keywords: Alzheimer’s disease, amyloid-β, 20S proteasome, 19S regulator particle, 11S regulator

DOI: 10.3233/JAD-160491

Journal: Journal of Alzheimer's Disease, vol. 54, no. 2, pp. 763-776, 2016