Cholesterol in brain disease: sometimes determinant and frequently implicated

• Published in: EMBO reports 2014-10, Vol.15 (10), p.1036-1052
• Main Authors: Martín, Mauricio G, Pfrieger, Frank, Dotti, Carlos G
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; brain disease; Cell Membrane - chemistry; Cell Membrane - metabolism; Cholesterol; Cholesterol - chemistry; Cholesterol - metabolism; cognition; EMBO21; EMBO24; EMBO27; Gonadal Steroid Hormones - chemistry; Gonadal Steroid Hormones - metabolism; Hormones; Human health and pathology; Humans; Huntington Disease - genetics; Huntington Disease - metabolism; Huntington Disease - pathology; Life Sciences; Lipid Metabolism; Mutation; Neurological disorders; Neurons - metabolism; Neurons - physiology; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Review; Reviews; Steroid hormones
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201439225

Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell–cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol‐related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease‐causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non‐hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function. Graphical Abstract Cholesterol is well known to be essential for normal brain and neuron function. This review discusses how defects in cholesterol metabolism might contribute to neurological syndromes, either as a cause or a consequence of these serious illnesses.