Neurodegenerative diseases, infectious pathologies and liquid crystals: Hypothesis of a common information vector involving a multidisciplinary approach

Abstract

The existence of an information vector common to very different pathologies is the hypothesis of one of us, the argumentation and discussion of which we present here. It is a mesomorphic state of material called liquid crystal. The liquid-ordered (Lo) phase, made up of membrane rafts mediated by cholesterol, lies at the center of our concept. This mesophase is either preexistent and then modified by the pathogenic process, or initiated by the latter. The most notable disorders involved are Alzheimer's, Parkinson's, Charcot and Creutzfeldt-Jakob diseases, flu-like illnesses and acquired immunodeficiency syndrome (AIDS), although this list may well be extended to include other anisotropic, birefringent amyloid proteinopathies, which have properties compatible with those of liquid crystals. Incidentally, numerous conventional infectious pathologies can also induce a mesomorphic state in cell membranes. It has already been established that mesophases contain the chemical information transmitted from the intramolecular microscopic level, where covalent bonds are applied. Information is then transmitted at the intermolecular macroscopic level, where it is made up of informed, self-organized collections. Electrostatic interactions, coordination of metallic ions, van der Waals forces and donor-acceptor interactions of hydrogen bonding all come into play. These reactions are produced notably in the nanodomains enriched by cholesterol and sphingolipids. Lipids in the cell membrane are where the phase separations favoring elastic hydrodynamic instabilities conducive to the Lo phase take place. In addition, perturbations of the mesomorphic states of membrane rafts due, for example, to lipid dysfunction-even mild ones-with an intracerebral or generalized location could bring about a displacement of thermodynamic equilibrium favoring the initiation and progression of the pathologies under consideration here. Indeed, the most recent work has rendered our hypothesis highly probable. Moreover, our hypothesis is supported by medical and biological observations arising essentially from biophysics and widely documented in the literature. Thus, these facts expand the number of diagnostic and therapeutic perspectives that could be evoked and perhaps even demand exploration.

Oncogenesis, lipids rafts and liquid crystals: A nanoscopic supplementary field for applied researches and a new hope of advances in cancer

“…Aggressive de-novo lipogenesis originating in endoplasmic reticulum (ER) lipid rafts is accompanied by imbalance between long-chain saturated fatty acids and shorter-chain non-saturated fatty acids, leading to lipotoxicity [ 20 , 24 ]. It is cholesterol [ 2 , 10 , 25 ] that organizes membrane lipid distribution and phase separation, leading to the “Lo state” constituting lipid rafts. The association of cholesterol and saturated fatty acid chain lipids determines the conditions for localized Lo state formation [10] .…”

“…This pathway is entirely dependent on Lo membrane nanodomains, initiating multiple downstream intracellular pathways [ 2 , 17 , 20 , 21 , 25 , 38 ]. The LC structure of the lipid raft determines the multiple interactions within the pathway and their connections with the other pathways referred to above.…”

“…It is noteworthy that the structure of the ER membrane shows an LC state; via the structure-function relationship, this mesophase thus directly controls the above processes. The SREBP-SCAP-INSIG, HMG-CoA reductase pathway is an example of the link between an ER transmembrane regulatory protein and expression of genes involved in cholesterol synthesis and hydrolysis [2] .…”

“…One of us put forward the idea of an information vector common to neurodegenerative and infectious diseases comprising membrane LCs in an ordered liquid (or “Lo”) phase, mediated by cholesterol in lipid rafts. This hypothesis has been recently demonstrated, and is presently considered as a theory [2] .…”

“…We have reported a series of studies [2] , ready to be implemented that could launch this new line of research, and informed and adaptive chemistry [42] can now perform therapeutic experiments in animals. For results to come quickly, however, an interdisciplinary approach is needed to truly combine fields of knowledge, rather than simply juxtaposing them as is frequently the case [2] .…”