In this section
@article{Stefaniak:2026:10.1111/cbdd.70332,
author = {Stefaniak, E and Cui, B and Yan, X and Sun, K and Teng, X and Ying, L},
doi = {10.1111/cbdd.70332},
journal = {Chemical Biology and Drug Design},
title = {Therapeutic peptide SS-31 modulates membrane binding and aggregation of α-synuclein and restores impaired mitochondrial function},
url = {http://dx.doi.org/10.1111/cbdd.70332},
volume = {107},
year = {2026}
}
TY - JOUR
AB - Membrane binding and aggregation properties of α-synuclein are closely associated with Parkinson's disease and a class of related syndromes named as synucleinopathy. This study explored the potential of SS-31 (Elamipretide), a therapeutic tetrapeptide with alternating cationic and aromatic residues and known properties of mitochondrial inner membrane binding and oxidative stress reduction, in modulating α-synuclein interaction with the lipid membranes and mitigating the impairment of mitochondrial function induced by α-synuclein oligomers. It was demonstrated by both fluorescence correlation spectroscopy and fluorescence anisotropy that SS-31 displaces both wild-type and N-terminal acetylated α-synuclein from negatively charged small unilamellar vesicles in a dose-dependent manner. Thioflavin-T assay and transmission electron microscopy showed that SS-31 inhibits membrane-induced α-synuclein aggregation and alters the morphology of α-synuclein fibrils. Moreover, MTT assay and Seahorse Mito Stress Test indicated that SS-31 enhances cell viability and restores impaired mitochondrial function in α-synuclein oligomer-treated neuroblastoma cells. Finally, confocal imaging revealed that SS-31 hinders cellular uptake of α-synuclein oligomers, possibly by modifying cell membrane electrostatics. These findings suggest that SS-31 potentially attenuates α-synuclein induced mitochondrial impairment via its interaction with the lipid membranes, justifying further development of a peptide-based intervention against α-synuclein mediated pathology.
AU - Stefaniak,E
AU - Cui,B
AU - Yan,X
AU - Sun,K
AU - Teng,X
AU - Ying,L
DO - 10.1111/cbdd.70332
PY - 2026///
SN - 1747-0277
TI - Therapeutic peptide SS-31 modulates membrane binding and aggregation of α-synuclein and restores impaired mitochondrial function
T2 - Chemical Biology and Drug Design
UR - http://dx.doi.org/10.1111/cbdd.70332
UR - https://onlinelibrary.wiley.com/doi/full/10.1111/cbdd.70332
VL - 107
ER -