Drug Treatment Corrects Autism Symptoms in Mouse Model

ucsdhealthsciences:

Autism results from abnormal cell communication. Testing a new theory, researchers at the University of California, San Diego School of Medicine have used a newly discovered function of an old drug to restore cell communications in a mouse model of autism, reversing symptoms of the devastating disorder.

The findings are published in the March 13, 2013 issue of the journal PLOS ONE.

“Our (cell danger) theory suggests that autism happens because cells get stuck in a defensive metabolic mode and fail to talk to each other normally, which can interfere with brain development and function,” said Robert Naviaux, MD, PhD, professor of medicine and co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego. “We used a class of drugs that has been around for almost a century to treat other diseases to block the ‘danger’ signal in a mouse model, allowing cells to return to normal metabolism and restore cell communication.”

“Of course, correcting abnormalities in a mouse is a long way from a cure for humans,” said Naviaux, “but we are encouraged enough to test this approach in a small clinical trial of children with autism spectrum disorder in the coming year. This trial is still in the early stages of development. We think this approach – called antipurinergic therapy or APT – offers a fresh and exciting new path that could lead to development of a new class of drugs to treat autism.”

Autism spectrum disorders (ASDs) are complex disorders defined by abnormalities in the development of language, social and repetitive behaviors. Hundreds of different genetic and environment factors are known to confer risk.  In this study, nearly a dozen UC San Diego scientists from different disciplines collaborated to find a unifying mechanism that explains autism.  Their work is the result of one of just three international “Trailblazer” awards given by the group Autism Speaks in 2011.

Describing a completely new theory for the origin and treatment of autism using APT, Naviaux and colleagues introduce the concept that a large majority of both genetic and environmental causes for autism act by producing a sustained cell danger response – the metabolic state underlying innate immunity and inflammation.

“When cells are exposed to classical forms of dangers, such as a virus, infection or toxic environmental substance, a defense mechanism is activated,” Naviaux explained.  “This results in changes to metabolism and gene expression, and reduces the communication between neighboring cells. Simply put, when cells stop talking to each other, children stop talking.”

Since mitochondria – the so-called “power plants” of the cell – play a central role in both infectious and non-infectious cellular stress, innate immunity and inflammation, Naviaux and colleagues searched for a signaling system in the body that was both linked to mitochondria and critical for innate immunity.  They found it in extracellular nucleotides like adenosine triphosphate (ATP) and other mitokines – signaling molecules made by distressed mitochondria. These mitokines have separate metabolic functions outside of the cell where they bind to and regulate receptors present on every cell of the body.  Fifteen types of purinergic receptors are known to be stimulated by these extracellular nucleotides, and the receptors are known to control a broad range of biological characteristics with relevance to autism.

The researchers tested suramin – a well-known inhibitor of purinergic signaling used medically for the treatment of African sleeping sickness since shortly after it was synthesized in 1916 – in mice.  They found that this APT mediator corrected autism-like symptoms in the animal model, even if the treatment was started well after the onset of symptoms.  The drug restored 17 types of multi-symptom abnormalities including normalizing brain synapse structure, cell-to-cell signaling, social behavior, motor coordination and normalizing mitochondrial metabolism.

“The striking effectiveness shown in this study using APT to ‘reprogram’ the cell danger response and reduce inflammation showcases an opportunity to develop a completely new class of anti-inflammatory drugs to treat autism and several other disorders,” Naviaux said. 

Inspiration needed.

Please, help!

Chemical Recipes no.1

Trind Nail Repair

  • Maximum 75%: organic solvents (mixture of ethyl acetate, butyl acetate, isopropyl alcohol,n-butyl alcohol,toluene).
  • Maximum 30%: non-volatile addtile additives, film-forming components (e.g.nitrocellulose), softeners (e.g. dibutyl phthalate), Polymer resins, thixotropic agents (e.g. stearalkonium hectorite).
  • Maximum 5% UV filters, camphor, titanium dioxid.
  • Maximum 2,5% formaldehyde.

http://www.trind.com/Trind/MediaLibrary/3/206//mlt_800_600_NailRepair.jpeg

This product has been in my beauty case forever. It’s tremendously effective to fragile nails, making them strong and flexible.

On the other hand, it does contain few interestig chemicals.

First, I couldn’t help but notice the presence of formaldehyde. Formaldehyde is the simplest aldehyde, and it is known to be a human carcinogen. Injesting 30 mL (1 oz.) of a solution containing 37% formaldehyde has been reported to cause death in an adult human.  On the other hand, since the bottle only contains  9 mL of product, it is unlikely that such small amount would harm you.

Toluene  is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. It can cause tiredness, confusion, weakness, drunken-type actions, memory loss, nausea. It is, however, less toxic than benzene, a known human carcinogen.

I hope it is clear to you, my dear readers, that toxicity is referred to this substanced used at a pure state, or in solutions at high concentration.

I’m not here to tell you not to wear any make up. What I’m trying to do with this column is to help people knowing what they put on their faces every day, with an educational intent.

neurosciencestuff:

Suicidal behaviour is a disease, psychiatrists argue
As suicide rates climb steeply in the US a growing number of psychiatrists are arguing that suicidal behaviour should be considered as a disease in its own right, rather than as a behaviour resulting from a mood disorder.
They base their argument on mounting evidence showing that the brains of people who have committed suicide have striking similarities, quite distinct from what is seen in the brains of people who have similar mood disorders but who died of natural causes.
Suicide also tends to be more common in some families, suggesting there may be genetic and other biological factors in play. What’s more, most people with mood disorders never attempt to kill themselves, and about 10 per cent of suicides have no history of mental disease.
The idea of classifying suicidal tendencies as a disease is being taken seriously. The team behind the fifth edition of the Diagnostic Standards Manual (DSM-5) – the newest version of psychiatry’s “bible”, released at the American Psychiatric Association’s meeting in San Francisco this week – considered a proposal to have “suicide behaviour disorder” listed as a distinct diagnosis. It was ultimately put on probation: put into a list of topics deemed to require further research for possible inclusion in future DSM revisions.
Another argument for linking suicidal people together under a single diagnosis is that it could spur research into the neurological and genetic factors they have in common. This could allow psychiatrists to better predict someone’s suicide risk, and even lead to treatments that stop suicidal feelings.
Signs in the brain
Until the 1980s, the accepted view in psychiatry was that people who committed suicide were, by definition, depressed. But that view began to change when autopsies revealed distinctive features in the brains of people who had committed suicide, including structural changes in the prefrontal cortex – which controls high-level decision-making – and altered levels of the neurochemical serotonin. These characteristics appeared regardless of whether the people had suffered from depression, schizophrenia, bipolar disorder, or no disorder at all (Brain Research).
But there is no single neurological cause of suicide, says Gustavo Turecki of McGill University in Montreal. What is more likely, he says, is that environmental factors trigger a series of changes in the brains of people who are already genetically prone to suicide, contributing to a constellation of factors that ultimately increase risk. These factors include a history of abuse as a child, post-traumatic stress disorder, long periods of anxiety, or sleep deprivation.
The search for more of these factors is complicated by the rarity of brain samples from suicide victims and the lack of an animal model – humans are unique in their wilful ability to end their lives. But some studies are yielding insights. For example, when people with bipolar disorder who have previously attempted suicide begin taking lithium, they tend to stop attempting suicide even if the drug has no effect on their other symptoms. This suggests that the drug may be acting on neural pathways that specifically influence suicidal tendencies (Annual Review of Pharmacology and Toxicology).
In the genes?
There is also growing evidence that genetics plays a role. For example, according to one study, identical twins share suicidal tendencies 15 per cent of the time, compared with 1 per cent in non-identical twins (Journal of Affective Disorders). And a study of adopted people who had committed suicide found that their biological relatives were six times more likely to commit suicide than members of the family that adopted them (American Journal of Medical Genetics).
A number of individual genes have been linked to suicide, such as those involved in the brain’s response to mood-lifting serotonin, and a signalling molecule called brain-derived neurotrophic factor (BDNF), which regulates the brain’s response to stress. Both tend to be suppressed in the brains of people who committed suicide, regardless of what mental disorder they had. Other studies of post-mortem brains have found that people who commit suicide after a bout of depression have different brain chemistry from depressed people who die of natural causes.
A study by Turecki, published this month, compared the brains of 46 people who had committed suicide with those of 16 people who died of natural causes. In the first group, 366 genes, mostly related to learning and memory, had a different set of epigenetic markers – chemical switches that turn genes on and off (American Journal of Psychiatry). The results are complicated by the fact that many of the people who committed suicide suffered from mental disorders, but Turecki says that suicide, rather than having a mental disorder, was the only significant predictor for these specific epigenetic changes.
No one yet knows the mechanism through which environmental factors would alter these genes, although stress hormones such as cortisol may be playing a role.
Understanding risk
Ultimately, biological and genetic markers might allow psychiatrists to better predict which patients are most at risk of suicide. But David Brent of the University of Pittsburgh, Pennsylvania, cautions that even if we can one day use biomarkers to predict if someone will make a suicide attempt, they do not tell us when. “If clinicians are keeping an eye on a patient, they need to know if there’s imminent risk,” he says.
However, knowing someone’s long-term suicide risk may have important implications for how a doctor chooses to treat that person, says Jan Fawcett of the University of New Mexico in Albuquerque.
For instance, a doctor may decide not to prescribe certain antidepressants to a patient with these biomarkers, as many drugs are thought to increase suicide risk. Another question would be whether to commit a person to a mental hospital – a major decision, he says, as people are most likely to commit suicide right after being released from hospital (Archives of General Psychiatry).
David Shaffer of Columbia University in New York, who was a member of the DSM-V working group, says that suicide behaviour disorder is “very much in the spirit” of the new Research Domain Criteria system that the US National Institute of Mental Health proposed as an alternative diagnosis standard to DSM-V. Rather than diagnosing people with depression or bipolar disorder, for example, the NIMH wants mental disorders to be diagnosed and treated more objectively using patients’ behaviour, genetics and neurobiology.
Ultimately, says Nader Perroud of the University of Geneva in Switzerland, if suicidal behaviour is considered as a disease in its own right, it will become possible to conduct more focused, evidence-based research on it and medications that treat it effectively. “We might be able to find a proper treatment for suicidal behaviour.”
(Image: GETTY)

neurosciencestuff:

Suicidal behaviour is a disease, psychiatrists argue

As suicide rates climb steeply in the US a growing number of psychiatrists are arguing that suicidal behaviour should be considered as a disease in its own right, rather than as a behaviour resulting from a mood disorder.

They base their argument on mounting evidence showing that the brains of people who have committed suicide have striking similarities, quite distinct from what is seen in the brains of people who have similar mood disorders but who died of natural causes.

Suicide also tends to be more common in some families, suggesting there may be genetic and other biological factors in play. What’s more, most people with mood disorders never attempt to kill themselves, and about 10 per cent of suicides have no history of mental disease.

The idea of classifying suicidal tendencies as a disease is being taken seriously. The team behind the fifth edition of the Diagnostic Standards Manual (DSM-5) – the newest version of psychiatry’s “bible”, released at the American Psychiatric Association’s meeting in San Francisco this week – considered a proposal to have “suicide behaviour disorder” listed as a distinct diagnosis. It was ultimately put on probation: put into a list of topics deemed to require further research for possible inclusion in future DSM revisions.

Another argument for linking suicidal people together under a single diagnosis is that it could spur research into the neurological and genetic factors they have in common. This could allow psychiatrists to better predict someone’s suicide risk, and even lead to treatments that stop suicidal feelings.

Signs in the brain

Until the 1980s, the accepted view in psychiatry was that people who committed suicide were, by definition, depressed. But that view began to change when autopsies revealed distinctive features in the brains of people who had committed suicide, including structural changes in the prefrontal cortex – which controls high-level decision-making – and altered levels of the neurochemical serotonin. These characteristics appeared regardless of whether the people had suffered from depression, schizophrenia, bipolar disorder, or no disorder at all (Brain Research).

But there is no single neurological cause of suicide, says Gustavo Turecki of McGill University in Montreal. What is more likely, he says, is that environmental factors trigger a series of changes in the brains of people who are already genetically prone to suicide, contributing to a constellation of factors that ultimately increase risk. These factors include a history of abuse as a child, post-traumatic stress disorder, long periods of anxiety, or sleep deprivation.

The search for more of these factors is complicated by the rarity of brain samples from suicide victims and the lack of an animal model – humans are unique in their wilful ability to end their lives. But some studies are yielding insights. For example, when people with bipolar disorder who have previously attempted suicide begin taking lithium, they tend to stop attempting suicide even if the drug has no effect on their other symptoms. This suggests that the drug may be acting on neural pathways that specifically influence suicidal tendencies (Annual Review of Pharmacology and Toxicology).

In the genes?

There is also growing evidence that genetics plays a role. For example, according to one study, identical twins share suicidal tendencies 15 per cent of the time, compared with 1 per cent in non-identical twins (Journal of Affective Disorders). And a study of adopted people who had committed suicide found that their biological relatives were six times more likely to commit suicide than members of the family that adopted them (American Journal of Medical Genetics).

A number of individual genes have been linked to suicide, such as those involved in the brain’s response to mood-lifting serotonin, and a signalling molecule called brain-derived neurotrophic factor (BDNF), which regulates the brain’s response to stress. Both tend to be suppressed in the brains of people who committed suicide, regardless of what mental disorder they had. Other studies of post-mortem brains have found that people who commit suicide after a bout of depression have different brain chemistry from depressed people who die of natural causes.

A study by Turecki, published this month, compared the brains of 46 people who had committed suicide with those of 16 people who died of natural causes. In the first group, 366 genes, mostly related to learning and memory, had a different set of epigenetic markers – chemical switches that turn genes on and off (American Journal of Psychiatry). The results are complicated by the fact that many of the people who committed suicide suffered from mental disorders, but Turecki says that suicide, rather than having a mental disorder, was the only significant predictor for these specific epigenetic changes.

No one yet knows the mechanism through which environmental factors would alter these genes, although stress hormones such as cortisol may be playing a role.

Understanding risk

Ultimately, biological and genetic markers might allow psychiatrists to better predict which patients are most at risk of suicide. But David Brent of the University of Pittsburgh, Pennsylvania, cautions that even if we can one day use biomarkers to predict if someone will make a suicide attempt, they do not tell us when. “If clinicians are keeping an eye on a patient, they need to know if there’s imminent risk,” he says.

However, knowing someone’s long-term suicide risk may have important implications for how a doctor chooses to treat that person, says Jan Fawcett of the University of New Mexico in Albuquerque.

For instance, a doctor may decide not to prescribe certain antidepressants to a patient with these biomarkers, as many drugs are thought to increase suicide risk. Another question would be whether to commit a person to a mental hospital – a major decision, he says, as people are most likely to commit suicide right after being released from hospital (Archives of General Psychiatry).

David Shaffer of Columbia University in New York, who was a member of the DSM-V working group, says that suicide behaviour disorder is “very much in the spirit” of the new Research Domain Criteria system that the US National Institute of Mental Health proposed as an alternative diagnosis standard to DSM-V. Rather than diagnosing people with depression or bipolar disorder, for example, the NIMH wants mental disorders to be diagnosed and treated more objectively using patients’ behaviour, genetics and neurobiology.

Ultimately, says Nader Perroud of the University of Geneva in Switzerland, if suicidal behaviour is considered as a disease in its own right, it will become possible to conduct more focused, evidence-based research on it and medications that treat it effectively. “We might be able to find a proper treatment for suicidal behaviour.”

(Image: GETTY)

Internships, Obsessive writing, and Chemical Recipes

Hi guys! Long time, no see!

I’ve been very busy with my internship (more of this later on), and my thesis, but I haven’t forgotten you!

I’ve had an idea whirling in my mind for quite some time now. This idea led me to explore the infamous INCI of approximately every beauty product I own, and to find the chemical wonders behind them. Needless to say, I made few scary discoveries! 

As a result of these wanderings, I proudly present you my new column, Chemical Recipes!

I’m currently working on my first entry, which will be about a daily use nail product.

Stay tuned!

PS: in the meantime, why don’t you like LabCoat Girl’s page on Facebook?

Brain Tricks - This Is How Your Brain Works (by AsapSCIENCE)

Molecule of the Week #42
Cholesterol, from the Greek chole- (bile) and stereos (solid) followed by the chemical suffix-ol for an alcohol, is an organic molecule. It is a sterol (or modified steroid), It is an essential structural component of animal cell membranes that is required to establish propermembrane permeability and fluidity.
In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D. Cholesterol is the principalsterol synthesized by animals; in vertebrates it is formed predominantly in the liver. It is almost completely absent among prokaryotes (i.e., bacteria).
François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound “cholesterine”.
Since cholesterol is essential for all animal life, each cell synthesizes it from simpler molecules, a complex 37-step process which starts with the intracellular protein enzymeHMG-CoA reductase. However, normal and especially high levels of fats (including cholesterol) in the blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis.
For a man of about 68 kg (150 pounds), typical total body-cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g, primarily located within all the membranes of all the cells of the body. Typical daily dietary intake of additional cholesterol, in the United States, is 200–300 mg.
However, most ingested cholesterol is esterified, and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis. For these reasons, cholesterol intake in food has little, if any, effect on total body cholesterol content or concentrations of cholesterol in the blood.
Cholesterol is recycled. The liver excretes it in a non-esterified form (via bile) into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.
Some plants make cholesterol in very small amounts. Plants manufacture phytosterols(substances chemically similar to cholesterol produced within plants), which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption. When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the GI tract, an important protective mechanism.
Cholesterol is required to build and maintain membranes; it modulates membrane fluidityover the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulkysteroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which reduces membrane fluidity. The structure of the tetracyclic ring of cholesterol contributes to the decreased fluidity of the cell membrane as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes, protons, (positive hydrogen ions) and sodium ions.
Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolaeand clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. Lipid raft formation brings receptor proteins in close proximity with high concentrations of second messenger molecules. In many neurons, a myelin sheath, rich in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.
Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. Cholesterol is an important precursor molecule for the synthesis of vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone,estrogens, and testosterone, and their derivatives.
Some research indicates cholesterol may act as an antioxidant.
All animal cells manufacture cholesterol with relative production rates varying by cell type and organ function. About 20–25% of total daily cholesterol production occurs in the liver; other sites of higher synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are hydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This is the regulated, rate-limiting and irreversible step in cholesterol synthesis and is the site of action for the statin drugs (HMG-CoA reductase competitive inhibitors).
Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require ATP. Mevalonate is decarboxylated toisopentenyl pyrophosphate, which is a key metabolite for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is converted to cholesterol through a 19-step process.
Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism.

Molecule of the Week #42

Cholesterol, from the Greek chole- (bile) and stereos (solid) followed by the chemical suffix-ol for an alcohol, is an organic molecule. It is a sterol (or modified steroid), It is an essential structural component of animal cell membranes that is required to establish propermembrane permeability and fluidity.

In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D. Cholesterol is the principalsterol synthesized by animals; in vertebrates it is formed predominantly in the liver. It is almost completely absent among prokaryotes (i.e., bacteria).

François Poulletier de la Salle first identified cholesterol in solid form in gallstones in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound “cholesterine”.

Since cholesterol is essential for all animal life, each cell synthesizes it from simpler molecules, a complex 37-step process which starts with the intracellular protein enzymeHMG-CoA reductase. However, normal and especially high levels of fats (including cholesterol) in the blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis.

For a man of about 68 kg (150 pounds), typical total body-cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g, primarily located within all the membranes of all the cells of the body. Typical daily dietary intake of additional cholesterol, in the United States, is 200–300 mg.

However, most ingested cholesterol is esterified, and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis. For these reasons, cholesterol intake in food has little, if any, effect on total body cholesterol content or concentrations of cholesterol in the blood.

Cholesterol is recycled. The liver excretes it in a non-esterified form (via bile) into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.

Some plants make cholesterol in very small amounts. Plants manufacture phytosterols(substances chemically similar to cholesterol produced within plants), which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption. When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the GI tract, an important protective mechanism.

Cholesterol is required to build and maintain membranes; it modulates membrane fluidityover the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulkysteroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which reduces membrane fluidity. The structure of the tetracyclic ring of cholesterol contributes to the decreased fluidity of the cell membrane as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar. In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes, protons, (positive hydrogen ions) and sodium ions.

Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolaeand clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. Lipid raft formation brings receptor proteins in close proximity with high concentrations of second messenger molecules. In many neurons, a myelin sheath, rich in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.

Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. Cholesterol is an important precursor molecule for the synthesis of vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone,estrogens, and testosterone, and their derivatives.

Some research indicates cholesterol may act as an antioxidant.

All animal cells manufacture cholesterol with relative production rates varying by cell type and organ function. About 20–25% of total daily cholesterol production occurs in the liver; other sites of higher synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are hydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This is the regulated, rate-limiting and irreversible step in cholesterol synthesis and is the site of action for the statin drugs (HMG-CoA reductase competitive inhibitors).

Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require ATP. Mevalonate is decarboxylated toisopentenyl pyrophosphate, which is a key metabolite for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is converted to cholesterol through a 19-step process.

Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism.