title: Noise in multiple sclerosis: unwanted and necessary.
abstract: As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression "noise") can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy.
authors.affiliation: Department of Physics, Sapienza University of Rome Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Bordi
authors.affiliation: Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome Rome, Italy ; Neuroimmunology Unit, Fondazione Santa Lucia, (I.R.C.C.S.) Rome, Italy.
authors.forename: Vito A G
authors.initials: VA
authors.lastname: Ricigliano
authors.affiliation: Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome Rome, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Umeton
authors.affiliation: Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ristori
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grassi
authors.affiliation: Department of Physics, Sapienza University of Rome Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.affiliation: Department of Physics, Sapienza University of Rome Rome, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sutera
authors.affiliation: Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), Centre for Experimental Neurological Therapies (CENTERS), Sapienza University of Rome Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti