Next Article in Journal
Transcriptomic Analysis Reveals the Wound Healing Activity of Mussel Myticin C
Previous Article in Journal
Osmolytes: A Possible Therapeutic Molecule for Ameliorating the Neurodegeneration Caused by Protein Misfolding and Aggregation
Open AccessArticle

Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity

1
Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden
2
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, 21428 Malmö, Sweden
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 134; https://doi.org/10.3390/biom10010134
Received: 4 November 2019 / Revised: 10 January 2020 / Accepted: 12 January 2020 / Published: 14 January 2020
Apolipoprotein E (ApoE) has become a primary focus of research after the discovery of its strong linkage to Alzheimer’s disease (AD), where the ApoE4 variant is the highest genetic risk factor for this disease. ApoE is commonly found in amyloid deposits of different origins, and its interaction with amyloid-β peptide (Aβ), the hallmark of AD, is well known. However, studies on the interaction of ApoEs with other amyloid-forming proteins are limited. Islet amyloid polypeptide (IAPP) is an amyloid-forming peptide linked to the development of type-2 diabetes and has also been shown to be involved in AD pathology and vascular dementia. Here we studied the impact of ApoE on IAPP aggregation and IAPP-induced toxicity on blood vessel pericytes. Using both in vitro and cell-based assays, we show that ApoE efficiently inhibits the amyloid formation of IAPP at highly substoichiometric ratios and that it interferes with both nucleation and elongation. We also show that ApoE protects the pericytes against IAPP-induced toxicity, however, the ApoE4 variant displays the weakest protective potential. Taken together, our results suggest that ApoE has a generic amyloid-interfering property and can be protective against amyloid-induced cytotoxicity, but there is a loss of function for the ApoE4 variant.
Keywords: apolipoprotein E; IAPP amyloid; Thioflavin T; pericytes; cytotoxicity apolipoprotein E; IAPP amyloid; Thioflavin T; pericytes; cytotoxicity
Show Figures

Graphical abstract

MDPI and ACS Style

Gharibyan, A.L.; Islam, T.; Pettersson, N.; Golchin, S.A.; Lundgren, J.; Johansson, G.; Genot, M.; Schultz, N.; Wennström, M.; Olofsson, A. Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity. Biomolecules 2020, 10, 134.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop