Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy

New Insights into Multiple Sclerosis Mechanisms: Lipids on the Track to Control Inflammation and Neurodegeneration

“…Plasma concentration of 24(S)-OHC depends on the balance between its cerebral production—proportionally to the number of metabolically active neurons in the CNS—and hepatic elimination [ 49 ]. Over-expression of neuronal cholesterol 24-hydroxylase, increased cholesterol turnover, dysfunction of BBB, and inflammation might result in increased or reduced level of 24(S)-OHC in the plasma in particular stages of MS, constituting a suitable biomarker of the disease activity [ 50 , 51 ].…”

“…Oxysterols constitute another group of lipids of potential relevance for MS progression studies. They might appear as markers of mitochondrial status as well as neuronal damage [ 50 ]. As mentioned above, mitochondrial dysfunction is one of the key factors in neurodegenerative process underlying MS progression.…”

“…It contributes to increase oxidative stress levels, i.e., by overproduction of ROS, which further promotes formation of oxidized lipids [ 147 ]. Several studies suggest that oxidative stress is associated with increased levels of oxysterols produced by auto-oxidation (7-KC, 7β-OHC) as well as by enzymatic reaction, 24(S)-OHC [ 48 ]; all of which are indicators of neurodegeneration in MS [ 50 ]. It was also reported that 24(S)-OHC, the marker reflecting the number of metabolically active neurons [ 50 ], can disrupt red-ox homeostasis of neurons and glial cells, favoring accumulation and peroxidation of lipids [ 148 ].…”

“…Several studies suggest that oxidative stress is associated with increased levels of oxysterols produced by auto-oxidation (7-KC, 7β-OHC) as well as by enzymatic reaction, 24(S)-OHC [ 48 ]; all of which are indicators of neurodegeneration in MS [ 50 ]. It was also reported that 24(S)-OHC, the marker reflecting the number of metabolically active neurons [ 50 ], can disrupt red-ox homeostasis of neurons and glial cells, favoring accumulation and peroxidation of lipids [ 148 ]. It is of note that cholesterol 24-hydroxylase promoter activity was induced by oxidative stress and a dexamethasome/IL-6 combined treatment [ 149 ].…”

“…Thus oxysterols, acting as LXR agonists, seem to be promising candidates for remyelination-inducing therapies. Indeed, some remyelination—beside suppressed chronic inflammatory injury—was seen after their administration in an animal model of EAE [ 50 ].…”