Neuroprotective sterols are a group of cholesterol-derived molecules, including cholesterol itself and its metabolic byproducts like oxysterols and neurosteroids, that exert beneficial effects on neuronal survival, function, and resilience against insults like oxidative stress or inflammation. These sterols are essential for maintaining the structural integrity of neural membranes and acting as signaling molecules that modulate neurotransmission and gene expression. Maintaining appropriate levels is crucial for long-term brain health and cognitive longevity.
Origin
This term combines ‘neuroprotective,’ meaning the ability to shield neurons from damage, with ‘sterols,’ the class of steroid alcohols that includes cholesterol. The concept is central to understanding the brain’s intrinsic defense mechanisms. In the domain of hormonal health, many neuroprotective sterols are synthesized locally in the brain (neurosteroids) and function as neuromodulators, often interacting with the same receptors as peripheral hormones.
Mechanism
The mechanism is multi-faceted: Cholesterol is critical for the formation of lipid rafts and synaptic vesicles, which are essential for efficient neurotransmission. Oxysterols, such as 24S-hydroxycholesterol, facilitate the removal of excess cholesterol, maintaining membrane homeostasis. Neurosteroids, such as allopregnanolone and dehydroepiandrosterone (DHEA), modulate the activity of neurotransmitter receptors like GABA-A and NMDA receptors, thereby influencing neuronal excitability and promoting cell survival and repair pathways. This collective sterol action is fundamental to neuronal resilience.
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