The DOI matches its Crossref record; 235 of the 235 references it cites were found in a registry or an index.
Cholesterol in brain disease: sometimes determinant and frequently implicated
Open accessAbstract
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.
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“As statins were designed to act primarily by inhibiting cholesterol synthesis, their beneficial effects in the Mecp2-deficient mouse presumably reflect other mechanisms of action given that brain cholesterol synthesis is already moderately suppressed in these mice (Orth and Bellosta, 2012; Martin et al., 2014).”
From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Martin et al., 2014
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“Myelin contains the majority (>80%) of the brain’s free cholesterol”
From TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge (2020) · cites this paper as Martín et al., 2014
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In the citing paper
“Nevertheless, diet-derived cholesterol cannot cross the BBB and cannot compensate the low cholesterol level in the brain [3,24].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [24]
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“The most severe mutations of this gene cause fetal or newborn death, while less severe variants cause developmental defects in specific organs such as facial and cranial malformations, hypospadia or complete gonadal absence [24].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [24]
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“Cholesterol has been implied in the production and clearance of beta amyloid [24].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [24]
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“Disruption of cholesterol homeostasis has also been shown to perturb cell-autonomous and non-cell-autonomous functions, including inhibition of crucial signaling pathways and cellular crosstalk (Bjorkhem and Meaney, 2004; Martin et al., 2014).”
From Sterol dysregulation in Smith–Lemli–Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk (2022) · cites this paper as Martin et al., 2014
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“These data reinforce the previously well-established link between brain cholesterol metabolism dysfunction and AD pathogenesis [42], by pointing to PCSK9 as an additional contributor to the neuronal degeneration occurring in this disease.”
From PCSK9 affects astrocyte cholesterol metabolism and reduces neuron cholesterol supplying in vitro: potential implications in Alzheimer’s disease (2022) · cites this paper as [42]
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TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge
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Metadata
- Authors
- Martín, M. G., Pfrieger, F., & Dotti, C. G.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Centre National de la Recherche Scientifique (FR)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Martín, Mauricio G
- Pfrieger, Frank
- Dotti, Carlos G
- Venue
- The EMBO Reports
- Published
- 2014-09-15
- Volume
- 15
- Issue
- 10
- Pages
- 1036-1052
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC4253844
- OpenAlex
- W2027703774
- Cited by
- 304
- References
- 235
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 31 · 2023: 42 · 2022: 40 · 2021: 27 · 2020: 30 · 2019: 24 · 2018: 25 · 2017: 12 · 2016: 16 · 2015: 10
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Lirias (submittedVersion)
- CONICET Digital (CONICET) (submittedVersion, cc-by-nc-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- brain cholesterol, cholesterol metabolism, Alzheimer's disease, Huntington's disease, Parkinson's disease, cognitive impairment, synaptic function, ion permeability, transmembrane signaling
- MeSH terms
- Alzheimer Disease, Cell Membrane, Cholesterol, Humans, Huntington Disease, Mutation, Neurons, Parkinson Disease, Gonadal Steroid Hormones, Lipid Metabolism
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