Advanced Innovative Amyloid Fibril Nanotechnological Applications: β-Sheet Proteins, Protein Aggregation, Cognitive Decline, Microbiome Regulated Tau Protein Release, Photo-Pharmacological Drug Regulation and Development of High Performance Surgical Adhesives

Abstract

Margaret M Smith and James Melrose

Amyloid self-assembled from amyloid peptides β-40 or β-42 is notorious due to the neurotoxic effects of β- oligomers in plaque and neurofibrillary tangles, neuronal dysfunction and diseases of cognitive decline such as Alzheimer’s, or Parkinson’s disease. This contrasts with so-called functional amyloids which are non-toxic ordered β-sheet molecular templates amenable to applications in tissue engineering. Long and hollow amyloid fibres, flattened tube and spiral ribbons have been used in engineering applications. Protein β-sheet core structures display diverse biological functionalities exploitable in futuristic self-assembling biomaterials revolutionizing nanotechnological developments in photopharmacology pain research, ultra- high performance surgical bioadhesives, and our understanding of amyloid fibril assembly. Use of nano-wires cast within hollow amyloid fibrils has advanced nano-electronics in next generation computers, biosensors, ultracapacitors, memristors, actuators and molecular switches. Amyloid fibrils have been used in photon capture light harvesting technologies in nano- photoelectronics, and photovoltaic photopharmacology futuristic nano-technological advances. A better understanding of amyloid fibril assembly processes may also uncover better ways to control the toxic build up of amyloid in brain tissues in diseases of cognitive decline. An innovative survey of over 1 million microbiome metabolites that regulate 300 G-protein coupled neuroreceptors and Tau microtubule dynamics show effects on amyloid fibrillogenesis. Some of these metabolites are absent in AD individuals prone to cognitive decline demonstrating the importance of the gut-brain axis in neuro-pathobiology. With the ever-expanding prevalence of cognitive diseases in ageing global populations a clear and present need exists to treat these conditions. A promising number of therapeutic interventions discussed herein warrant further exploration.

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