Depression, Diabetes and Dementia: Formaldehyde May Be a Common Causal Agent; Could Carnosine, a Pluripotent Peptide, Be Protective?

Copyright: © 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent studies have highlighted the possible involvement of formaldehyde in a number of age-associated phenomena, dementia, depression and diabetes (type-2). Papers by Li et al. [1,2], Cui et al. [3], Tong et al. [4,5] and Mei et al. [6] have shown an association between formaldehyde and age-related dysfunction such as glaucoma, stroke, Alzheimer's disease and memory decline. Furthermore, Tulpule and colleagues [7,8] have demonstrated that formaldehyde strongly stimulates glycolytic flux in astrocytes and neurones, implying its contribution to metabolic age-related dysfunction, (e.g. type-2 diabetes, memory loss and neurodegeneration). Formaldehyde is thought to induce macromolecular dysfunction, at least in part, via its ability to crosslink protein to DNA [9]. Although formaldehyde-induced toxicity is not an entirely a new idea, it has been suggested that the presence of formaldehyde in the brain has been overlooked as either causative or a consequence of other underlying and deleterious phenomena [10,11]. Furthermore, given that current research indicates that excessive glycolytic activity may be an important contributor to not only type-2 diabetes but also to neurodegenerative conditions, it is perhaps relevant to note that formate, a product of formaldehyde metabolism, has been shown to enhance glycolytic flux in cultured astrocytes and neurones but inhibit mitochondrial respiration [7,8]. Other studies have shown that formaldehyde's effects on norepinephrine are mediated by direct reaction with the hormone, thus decreasing hormone availability [6] and thereby contributing to age-related memory decline. It has been found that the carbonyl scavengers, aminoguanidine and resveratrol, are effective in suppressing the effects of formaldehyde [12], but due to its toxicity, aminoguanidine is unlikely to be employed therapeutically, and resveratrol has also been described as a formaldehyde donor [13]. The naturally-occurring, pluripotent dipeptide, carnosine can also suppress the cross-linking activity of formaldehyde [14], most probably by reacting directly with it. More recently, carnosine has been shown to be protective in rats exposed to formaldehyde [15]. It is also interesting to note that increased levels of endogenous formaldehyde are present in the brains of the senescence accelerated mouse strain, SAMP8, at 3 months of age [16]. In earlier studies, dietary supplementation with carnosine has been shown to delay the onset of age-related changes in another senescence accelerated mouse …