Small stress molecules inhibit aggregation and neurotoxicity of prion peptide 106-126.
In prion diseases, the posttranslational modification of host-encoded prion protein PrP(c) yields a high beta-sheet content modified protein PrP(sc), which further polymerizes into amyloid fibrils. PrP106-126 initiates the conformational changes leading to the conversion of PrP(c) to PrP(sc). Molecules that can defunctionalize such peptides can serve as a potential tool in combating prion diseases. In microorganisms during stressed conditions, small stress molecules (SSMs) are formed to prevent protein denaturation and maintain protein stability and function. The effect of such SSMs on PrP106-126 amyloid formation is explored in the present study using turbidity, atomic force microscopy (AFM), and cellular toxicity assay. Turbidity and AFM studies clearly depict that the SSMs-ectoine and mannosylglyceramide (MGA) inhibit the PrP106-126 aggregation. Our study also connotes that ectoine and MGA offer strong resistance to prion peptide-induced toxicity in human neuroblastoma cells, concluding that such molecules can be potential inhibitors of prion aggregation and toxicity.
Department of Chemical and Materials Engineering, Arizona State University, P.O. Box 876006, Tempe, AZ 85287, USA.
Mathumai
M
Kanapathipillai
Sook Hee
SH
Ku
Koyeli
K
Girigoswami
Chan Beum
CB
Park
D000599:Amino Acids, Diamino / Q000008:administration & dosage*; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005699:Galactosylceramides / Q000008:administration & dosage*; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000008:administration & dosage / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry*; D011328:Prions / Q000008:administration & dosage* / Q000737:chemistry*; D011485:Protein Binding
D000599:Amino Acids, Diamino; D005699:Galactosylceramides; D046912:Multiprotein Complexes; D009498:Neurotoxins; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); C045628:ectoine