Record Details

A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of @-synuclein oligomers

DIR@IMTECH: CSIR-Institute of Microbial Technology

View Archive Info
 
 
Field Value
 
Title A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of @-synuclein oligomers
 
Creator Pirhaghi, Mitra
Frank, Signe Andrea
Alam, Parvez
Nielsen, Janni
Sereikaite , Vita
Gupta, Arpit
Stromgaard, Kristian
Andreasen, Maria
Sharma, Deepak
Ali , Akbar Saboury
Otzen , Daniel Erik
 
Subject QR Microbiology
 
Description Parkinson's disease is a neurodegenerative movement disorder associated with the intracellular aggregation of α-synuclein (α-syn). Cytotoxicity is mainly associated with the oligomeric species (αSOs) formed at early stages in α-syn aggregation. Consequently, there is an intense focus on the discovery of novel inhibitors such as peptides to inhibit oligomer formation and toxicity. Here, using peptide arrays, we identified nine peptides with high specificity and affinity for αSOs. Of these, peptides p194, p235, and p249 diverted α-syn aggregation from fibrils to amorphous aggregates with reduced β-structures and increased random coil content. However, they did not reduce αSO cytotoxicity and permeabilization of large anionic unilamellar vesicles. In parallel, we identified a non-self-aggregating peptide (p216), derived from the cell-penetrating peptide penetratin, which showed 12-fold higher binding affinity to αSOs than to α-syn monomers (Kdapp 2.7 and 31.2 μM, respectively). p216 reduced αSOs-induced large anionic unilamellar vesicle membrane permeability at 10-1 to 10-3 mg/ml by almost 100%, was not toxic to SH-SY5Y cells, and reduced αSOs cytotoxicity by about 20%. We conclude that p216 is a promising starting point from which to develop peptides targeting toxic αSOs in Parkinson's disease.
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2022-12
 
Type Article
PeerReviewed
 
Relation https://www.sciencedirect.com/science/article/pii/S0021925822011310?via%3Dihub
http://crdd.osdd.net/open/3149/
 
Identifier Pirhaghi, Mitra and Frank, Signe Andrea and Alam, Parvez and Nielsen, Janni and Sereikaite , Vita and Gupta, Arpit and Stromgaard, Kristian and Andreasen, Maria and Sharma, Deepak and Ali , Akbar Saboury and Otzen , Daniel Erik (2022) A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of @-synuclein oligomers. Journal of Biological Chemistry, 298 (12). ISSN 0021-9258