Multiple sclerosis, extra-mitochondrial energy production in myelin and transgenerational effects of lead exposure: Possible connections

Abstract

The discovery of extra-mitochondrial aerobic ATP synthesis via oxidative phosphorylation in the myelin sheath suggests that this type of energy production is also relevant to the pathophysiology of multiple sclerosis (MS). Myelin is a site of intense heme synthesis. Environmental toxins can interfere with heme synthesis, the heavy metal lead (Pb) being of particular significance regarding this interaction. Exposure to Pb has been identified as one of the environmental factors associated with MS. Throughout history, humans have been exposed to Pb from a variety of sources. Particularly noteworthy is the intensive period of exposure during antiquity in the Roman Empire in Europe when many household items and other materials were made of Pb. MS has been shown to have a high prevalence in areas where Pb mining has occurred in the past. Here we present our hypothesis according to which Pb pollution could have induced an epigenetic transgenerational effect associated with enhanced susceptibility to aberrant autoimmune reactions, perhaps involving heme synthesis in myelin and a decreased ability to detoxify xenobiotics. Pb intoxication can induce an excessive degeneration of myelin, which, in hypersensitive subjects, may trigger an autoimmune response typical of MS.