Ocular protein optineurin shows reversibility from unfolded states and exhibits chaperone-like activity.

Optineurin (OPTN) is a multifunctional, ubiquitously expressed cytoplasmic protein, mutants of which are associated with primary open-angle glaucoma (POAG) and amyotrophic lateral sclerosis (ALS). The most abundant heat shock protein crystallin, known for its remarkable thermodynamic stability and chaperoning activity, allows ocular tissues to withstand stress. The presence of OPTN in ocular tissues is intriguing.

Specific keratinase derived designer peptides potently inhibit A aggregation resulting in reduced neuronal toxicity and apoptosis.

Compelling evidence implicates self-assembly of amyloid- (A) peptides into soluble oligomers and fibrils as a major underlying event in Alzheimer's disease (AD) pathogenesis. Herein, we employed amyloid-degrading keratinase (kerA) enzyme as a key A-binding scaffold to identify five keratinase-guided peptides (KgPs) capable of interacting with and altering amyloidogenic conversion of A The KgPs showed micromolar affinities with A and abolished its sigmoidal amyloidogenic transition, resulting in abrogation of fibrillogenesis. Comprehensive assessment using dynamic light scattering (DLS), atomic force microscopy (AFM) and Fourier-transform infrared (FTIR) spectroscopy showed that KgPs induced the formation of oligomers comparatively larger than the native A oligomers but with a significantly reduced cross- signature.