Marco Ruggiero

Title : Negative entropy-driven self-assembly of information-containing aperiodic crystals aimed at increasing brain entropy in the context of Alzheimer's disease, dementia and cognitive decline

Abstract:

The degree of brain entropy (BEN) is associated with different levels of consciousness. The entropic brain hypothesis contemplates that, within upper and lower cutoff points, beyond which consciousness may be significantly reduced or absent, the entropy of spontaneous cerebral activity represents a measure of the informational richness of conscious states. Consistent with this hypothesis, BEN increases during physiological development, and decreases during states of reduced consciousness, such as aging, Alzheimer's disease, dementia, and cognitive decline. Here, a biomolecular approach aimed at increasing BEN is described; this approach is based on negative entropy-driven self-assembly of two types of information-containing aperiodic crystals. The first type consists of crystals of poly-lysine and glutamic acid; the second type consists of crystals of sulfated polysaccharides containing fucose, galactose, xylose, arabinose and rhamnose, and lysine, alanine, tyrosine and cyanocobalamin. In the first type of crystals, poly-lysine constitutes a backbone for the establishment of electrostatic bonds between the positively charged amino groups of poly-lysine and the negatively charged acidic moiety of glutamic acid. In the second type of crystals, the mixture of lysine, alanine, tyrosine and cyanocobalamin is complexed, through formation of electrostatic bonds, with the acidic backbone constituted by the sulfated polysaccharides where the negatively charged sulfate ester and carboxylic groups of the polysaccharides bind to the positively charged moieties of the amino acids and cyanocobalamin. The two types of aperiodic crystals interact in a CO₂-enriched hydrophilic medium with the resulting self-assembly of complex structures composed of random-sized aperiodic crystals of [poly-lysine/glutamic acid], and [sulfated polysaccharides /lysine/alanine/tyrosine/cyanocobalamin]. Although the crystals are formed through negative entropy-driven self-assembly, because of their random-size and, therefore, random distribution of electrical charges on their molecular surface, they contain an elevated degree of information according to Shannon's entropy equation. An additional level of information derives from the chemical structure of fucose, an hexose deoxy sugar that is the constituent, in repetitive sequences, of the sulfated polysaccharides taking part in the formation of the aperiodic crystals. The chemical formula of fucose, C₆H₁₂O₅, highlights the presence of three delocalized pi orbital electrons among six carbon atoms forming "pi resonance clouds" conducive to quantum effects that are hypothesized to be at the basis of consciousness (Hameroff, 2022, Front Mol Neurosci). The aim of the approach described in this study is to increase richness of consciousness by increasing BEN. In disorders of consciousness where BEN is decreased such as aging, Alzheimer's disease, dementia, and cognitive decline, this approach restores physiological levels of consciousness as demonstrated by electroencephalography and clinical observations. In healthy individuals, it leads to higher states of consciousness that could be particularly evident, for example, during meditation or transcranial ultrasound stimulation (Sanguinetti et al., 2020, Front Hum Neurosci) as demonstrated by electroencephalography and individual reports.

Audience Take Away

• Explain how the audience will be able to use what they learn?
• The audience will be able to apply the concepts presented here in the treatment of Alzheimer's disease, dementia, and cognitive decline
• How will this help the audience in their job?
• The audience will be able to use innovative approaches for the treatment of Alzheimer's disease, dementia, and cognitive decline
• Does this provide a practical solution to a problem that could simplify or make a designer’s job more efficient?
• Yes, it does. The approaches and the solutions presented here will provide practical solutions aimed at treating Alzheimer's disease, dementia, and cognitive decline

Biography:

Marco Ruggiero, MD, PhD, worked as post-doc at Burroughs Wellcome Co. (1984) and as visiting scientist at the National Cancer Institute of the NIH (1987). He was appointed Professor of Molecular Biology at the University of Firenze, Italy, in 1992 where he worked until 2014. He published more than 240 scientific articles co-authored, among others, by scientist such as EG Lapetina, SA Aaronson, JH Pierce, PH Duesberg, HH Bauer, JJ Bradstreet, D Klinghardt. One of his articles in PNAS was sponsored by Nobel Laureate Sir John Vane. His current research interests are in immunotherapy, quantum biology and microbiome medicine.