Effect of osmolytes on in-vitro aggregation properties of peptides derived from TGFBIp.

Scientific Reports
Anandalakshmi VenkatramanJodhbir S Mehta

Abstract

Protein aggregation has been one of the leading triggers of various disease conditions, such as Alzheimer's, Parkinson's and other amyloidosis. TGFBI-associated corneal dystrophies are protein aggregation disorders in which the mutant TGFBIp aggregates and accumulates in the cornea, leading to a reduction in visual acuity and blindness in severe cases. Currently, the only therapy available is invasive and there is a known recurrence after surgery. In this study, we tested the inhibitory and amyloid dissociation properties of four osmolytes in an in-vitro TGFBI peptide aggregation model. The 23-amino acid long peptide (TGFBIp 611-633 with the mutation c.623 G>R) from the 4th FAS-1 domain of TGFBIp that rapidly forms amyloid fibrils was used in the study. Several biophysical methods like Thioflavin T (ThT) fluorescence, Circular Dichroism (CD), fluorescence microscopy and Transmission electron microscopy (TEM) were used to study the inhibitory and amyloid disaggregation properties of the four osmolytes (Betaine, Raffinose, Sarcosine, and Taurine). The osmolytes were effective in both inhibiting and disaggregating the amyloid fibrils derived from TGFBIp 611-633 c.623 G>R peptide. The osmolytes did not have an adverse toxic effect ...Continue Reading

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Citations

Jun 13, 2020·Nature Reviews. Disease Primers·Yu Qiang SohJodhbir S Mehta
Feb 13, 2021·The Journal of Physical Chemistry Letters·Kailash P PrajapatiKarunakar Kar
Aug 24, 2021·Computers in Biology and Medicine·Mihir DeshmukhEung Kweon Kim

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Methods Mentioned

BETA
protein folding
circular
electron microscopy
fluorescence microscopy
fluorescence assay
circular dichroism
transgenic
Assay
Transmission

Software Mentioned

SPSS Statistics
CDNN
Image J

Related Concepts