Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases
Sebastián García1,2, Virna Margarita Martín Giménez3, Feres José Mocayar Marón1,2, Russel J. Reiter4 and Walter Manucha1,2
1Institute of Pharmacology, Department of Pathology, School of Medical Sciences, Cuyo National University, 2Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Council of Scientific and Technological Research (CONICET), Mendoza, 3Institute of Research in Chemical Sciences, School of Chemical and Technological Sciences, Cuyo Catholic University, San Juan, Argentina and 4Department of Cellular and Structural Biology, University of Texas Health Science at San Antonio, San Antonio, TX, USA
Offprint requests to: Walter Manucha, Ph.D., Institute of Pharmacology, Department of Pathology, School of Medical Sciences, Cuyo National University, Mendoza, Argentina. e-mail: wmanucha@yahoo.com.ar
Summary. Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuro-inflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson's and Alzheimer's diseases. Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland. Histol Histopathol 35, 789-800 (2020)
Key words: Melatonin, Cannabinoids, Mitochondria, Inflammaging, Neuroinflammation, Neuroprotection
DOI: 10.14670/HH-18-212