Neural Regeneration Research (Jan 2021)
Inflammation/bioenergetics-associated neurodegenerative pathologies and concomitant diseases: a role of mitochondria targeted catalase and xanthophylls
Abstract
Various inflammatory stimuli are able to modify or even “re-program” the mitochondrial metabolism that results in generation of reactive oxygen species. In noncommunicable chronic diseases such as atherosclerosis and other cardiovascular pathologies, type 2 diabetes and metabolic syndrome, these modifications become systemic and are characterized by chronic inflammation and, in particular, “neuroinflammation” in the central nervous system. The processes associated with chronic inflammation are frequently grouped into “vicious circles” which are able to stimulate each other constantly amplifying the pathological events. These circles are evidently observed in Alzheimer's disease, atherosclerosis, type 2 diabetes, metabolic syndrome and, possibly, other associated pathologies. Furthermore, chronic inflammation in peripheral tissues is frequently concomitant to Alzheimer's disease. This is supposedly associated with some common genetic polymorphisms, for example, Apolipoprotein-E ε4 allele carriers with Alzheimer's disease can also develop atherosclerosis. Notably, in the transgenic mice expressing the recombinant mitochondria targeted catalase, that removes hydrogen peroxide from mitochondria, demonstrates the significant pathology amelioration and health improvements. In addition, the beneficial effects of some natural products from the xanthophyll family, astaxanthin and fucoxanthin, which are able to target the reactive oxygen species at cellular or mitochondrial membranes, have been demonstrated in both animal and human studies. We propose that the normalization of mitochondrial functions could play a key role in the treatment of neurodegenerative disorders and other noncommunicable diseases associated with chronic inflammation in ageing. Furthermore, some prospective drugs based on mitochondria targeted catalase or xanthophylls could be used as an effective treatment of these pathologies, especially at early stages of their development.
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