Related Experiment Video
Updated: Mar 12, 2026
08:59
Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
3.2K
Defective cholesterol metabolism in amyotrophic lateral sclerosis
Jonas Abdel-Khalik1, Eylan Yutuc1, Peter J Crick1
1Swansea University Medical School, Swansea, United Kingdom.
Journal of Lipid Research
|November 5, 2016
Summary
Cholesterol metabolism is altered in amyotrophic lateral sclerosis (ALS). This neurodegenerative disease shows impaired brain cholesterol removal and reduced neuroprotective metabolites, suggesting a defective bile acid pathway in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Biochemistry
- Metabolomics
Background:
- Cholesterol released from dying neurons in the central nervous system (CNS) may serve as a biomarker for neurodegeneration.
- Altered cholesterol levels are implicated in the prognosis of amyotrophic lateral sclerosis (ALS).
Purpose of the Study:
- To investigate cholesterol and its metabolite levels in serum and cerebrospinal fluid (CSF) of ALS patients and healthy controls.
- To determine if cholesterol metabolism is altered in ALS and could serve as a diagnostic or prognostic biomarker.
Main Methods:
- Quantification of over 40 sterols in serum and CSF samples from ALS patients and controls.
- Analysis of metabolite concentrations, normalized to cholesterol levels in CSF.
- Comparison of serum and CSF sterol profiles between patient and control groups.
Main Results:
- Elevated cholesterol concentrations were observed in the CSF of ALS patients.
- Specific cholesterol metabolites involved in bile acid biosynthesis (e.g., 3β,7α-dihydroxycholest-5-en-26-oic acid) were reduced in ALS CSF when normalized to cholesterol.
- (25R)26-hydroxycholesterol, a precursor metabolite, was reduced in the serum of ALS patients.
Conclusions:
- The acidic pathway of bile acid biosynthesis appears to be defective in the brain in ALS.
- This defect may lead to impaired cholesterol clearance in the CNS, potentially contributing to neurotoxicity.
- Reduced levels of neuroprotective cholesterol metabolites may further exacerbate neuronal damage in ALS.
Related Concept Videos
01:26Cross-bridge Cycle
124.1K
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
124.1K
03:03Amyloid Fibrils
12.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
12.5K
01:22Lysosomal Hydrolases
4.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.7K
01:20Myasthenia Gravis: Overview and Treatment
3.2K
Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which...
3.2K
01:24Overview of Lipid Metabolism
6.4K
Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
6.4K
01:26Chemical Synapses
12.3K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
12.3K