In a recent review published in the journal Experimental & Molecular Medicine , researchers reviewed available literature on the role and mechanisms (molecular and pathological) by which cholesterol imbalances in the brain contribute to neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). They review over 80 publications on critical mechanisms, including synaptic dysfunctions, oligomers of amyloid beta (Aβ) protein, protein clustering and membrane structure alterations, and α-synuclein aggregation. Their findings suggest that altered cholesterol synthesis and metabolism are shared features of most investigated neurodegenerative diseases.
While cholesterol-lowering drugs can partially reduce these diseases' risk, additional research is required to develop future targeted pharmacological interventions against these conditions. Cholesterol enhances and accelerates APP cleavage by Bace1, leading to increased Aβ oligomer and plaque formation. Cholesterol binds to Aβ and increases the resistance of Aβ fibrils and oligomers to degradation.
Cholesterol imbalance and high extracellular cholesterol levels can stimulate the production and accumulation of Aβ peptides, which cause Aβ oligomer formation and aggregation in the brain, resulting in neuronal damage. This image was created with BioRender.com.
Study: Cholesterol imbalance and neurotransmission defects in neurodegeneration . Background Cholesterol is a waxy,.