Polyamines and other biogenic amines at the molecular basis of low prevalence diseases

Abstract

Biogenic amines are amino acid-derived compounds involved in the most important physiological functions: cell proliferation and differentiation, immunity, neurotransmission and neuroendocrine system, fertility. Diseases are the result of unrecovered alterations in the balance of, at least, one of our physiological network modules. In addition to the most common diseases, there are described more than 6000 low prevalent/rare diseases (RD), most of them related to the any of the physiological processes mentioned above. Thus, the pleitropy of biogenic amines suggest they must be involved in wide spectrum of human RDs. Putative solutions for these orphan patients need efforts to integrate useful molecular, clinical and pharmacological information from other similar, but more prevalent pathologies. The major aim of our group is to contribute to this relational and integrative effort (Reyes-Palomares et al., 2013, PMID: 23437198). Arginine-derived polyamines (putrescine, spermidine and spermine) are absolutely required for cell proliferation. Thus, polyamine overproduction is related to cancer proliferation and progression, including rare neoplasias (i.e.: neuroblastoma). Polyamine synthesis also is a clear target to fight against protozoan infections (rare diseases in Europe). Impaired polyamine synthesis has been related to epithelial pathologies as psoriasis and hairless phenotypes. It is proven that spermine synthase deficit is in the origin of Snyder-Robinson syndrome (Pegg, 2014, PMID:24395705). Histamine is derived from histidine. It is considered a neurotransmitter and immune mediator also having roles in cell life and death equilibrium. In a recent review, using text-mining technologies, we locate more than 25 immune, inflammatory, neurological and neuroendocrine rare pathologies having histamine (and other biogenic amines, as serotonin and dopamine) as relevant elements in their origins and/or evolution (Pino-Ángeles et al., 2012, PMID: 22435405). In addition, we should also consider the histamine role played in malignant pathologies as mastocytosis, rare gastrointestinal carcinomas and fertility (Sánchez-Jiménez et al., 2013, PMID: 22435405). The gaps in our knowledge still are considerable (specially at the level of membrane-related biomolecular interactions), and further integrative efforts (including in silico-assisted approaches) are claimed to fill them, as this information may contribute to development of new and more efficient strategies of prevention and therapy for many biomedical problems (both prevalent and rare diseases), of course, after the appropriate pre-clinical validation and clinical trial phases. Funded by Ministerio de Economía y Competitividad (Grant SAF2011-26518 and contract from AMER Consortium, CDTI), Plan Andaluz de Investigación y Desarrollo (CVI-06585). CIBERER is an initiative of Instituto de Salud Carlos III.