Research highlights how cholesterol imbalances in the brain contribute to neurodegenerative diseases like Alzheimer's, Huntington's, and Parkinson's, suggesting targeted therapeutic interventions.
By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Aug 5 2024 In a recent review published in the journal Experimental & Molecular Medicine , researchers reviewed available literature on the role and mechanisms by which cholesterol imbalances in the brain contribute to neurodegenerative disorders such as Alzheimer's disease , Huntington's disease , and Parkinson's disease .
Background Cholesterol is a waxy, fat-like substance found in the cell membranes of all human cells. It plays an integral role in neuronal signaling and synaptic connections, especially in the brain. Notably, the brain contains between 20-25% of all the body's cholesterol reserves, making it the organ with the highest cholesterol concentration in the human body. Interestingly, peripheral cholesterol is incapable of crossing the blood-brain barrier .
Molecular mechanisms 1. Synaptic dysfunction – Cholesterol has been observed to comprise up to 80% of the plasma membrane of synapses and is essential in both their formation and function. Research has highlighted that cholesterol imbalances can significantly alter the ability of synapses to share neurotransmissions effectively, eventually resulting in neurodegenerative diseases.
4. α-syn aggregation – The genesis and progression of PD are characterized by the accumulation of misfolded α-syn proteins in Lewy bodies . The mechanistic underpinnings of this process are a consequence of α-syn binding to membrane lipids. Imbalanced cholesterol accelerates α-syn aggregation and LB formation, increasing PD risk.
Neurodegeneration Alzheimer's Disease Brain Cell Diet Drugs Huntington's Disease Medicine Membrane Metabolism Neurodegenerative Diseases Neurons Parkinson's Disease Pathology Protein Research
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