Domain-Independent Inhibition of CBP/p300 Attenuates alpha-Synuclein Aggregation

Show full item record



Hlushchuk , I , Ruskoaho , H , Domanskyi , A , Airavaara , M & Välimäki , M J 2021 , ' Domain-Independent Inhibition of CBP/p300 Attenuates alpha-Synuclein Aggregation ' , ACS chemical neuroscience , vol. 12 , no. 13 , pp. 2273-2279 .

Title: Domain-Independent Inhibition of CBP/p300 Attenuates alpha-Synuclein Aggregation
Author: Hlushchuk, Irena; Ruskoaho, Heikki; Domanskyi, Andrii; Airavaara, Mikko; Välimäki, Mika J.
Contributor organization: Division of Pharmacology and Pharmacotherapy
Drug Research Program
Regenerative pharmacology group
Institute of Biotechnology
Divisions of Faculty of Pharmacy
Neuroscience Center
Date: 2021-07-07
Language: eng
Number of pages: 7
Belongs to series: ACS chemical neuroscience
ISSN: 1948-7193
Abstract: Neurodegenerative diseases are associated with failed proteostasis and accumulation of insoluble protein aggregates that compromise neuronal function and survival. In Parkinson's disease, a major pathological finding is Lewy bodies and neurites that are mainly composed of phosphorylated and aggregated alpha-synuclein and fragments of organelle membranes. Here, we analyzed a series of selective inhibitors acting on multidomain proteins CBP and p300 that contain both lysine acetyltransferase and bromodomains and are responsible for the recognition and enzymatic modification of lysine residues. By using high-affinity inhibitors, A-485, GNE-049, and SGC-CBP30, we explored the role of two closely related proteins, CBP and p300, as promising targets for selective attenuation of alpha-synuclein aggregation. Our data show that selective CBP/p300 inhibitors may alter the course of pathological alpha-synuclein accumulation in primary mouse embryonic dopaminergic neurons. Hence, drug-like CBP/p300 inhibitors provide an effective approach for the development of high-affinity drug candidates preventing alpha-synuclein aggregation via systemic administration.
Subject: alpha-Synuclein
lysine acetyltransferase
Parkinson's disease
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
acschemneuro.1c00215.pdf 5.881Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record