Subscribe
The latest psychology and neuroscience discoveries.
My Account
  • Mental Health
  • Social Psychology
  • Cognitive Science
  • Psychopharmacology
No Result
View All Result
PsyPost
PsyPost
No Result
View All Result
Home Exclusive Mental Health

Can some types of fat protect us from brain disease?

by University of California at Berkeley
September 8, 2016
in Mental Health
Photo credit: Hyun-eui Kim

Photo credit: Hyun-eui Kim

[Subscribe to PsyPost on YouTube to stay up-to-date on the latest developments in psychology and neuroscience]

Share on FacebookShare on Twitter

An intriguing finding in nematode worms suggests that having a little bit of extra fat may help reduce the risk of developing some neurodegenerative diseases, such as Huntington’s, Parkinson’s and Alzheimer’s diseases.

What these illnesses have in common is that they’re caused by abnormal proteins that accumulate in or between brain cells to form plaques, producing damage that causes mental decline and early death.

Huntington’s disease, for example, is caused by aggregating proteins inside brain neurons that ultimately lead to motor dysfunction, personality changes, depression and dementia, usually progressing rapidly after onset in people’s 40s.

These protein aggregates – called Huntington’s aggregates – have been linked to problems with the repair system that nerve cells rely on to fix proteins that fold incorrectly: the cell’s so-called protein folding response. Misfolded proteins can make other proteins fold incorrectly, creating a chain reaction of misfolded proteins that form clumps that the cell can’t deal with.

When University of California, Berkeley, researchers perturbed the powerhouses of the cell, the mitochondria, in a strain of the nematode C. elegans that mimics Huntington’s disease, they saw their worms grow fat. They traced the effect to increased production of a specific type of lipid that, surprisingly, prevented the formation of aggregate proteins. The fat, they found, was required to turn on genes that protected the animals and cells from Huntington’s disease, revealing a new pathway that could be harnessed to treat the disease.

The same proved true in human cell lines cultured in a dish.

“We found that the worms and human cells were almost completely protected from the Huntington’s aggregates when we turned on this response,” said Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research in UC Berkeley’s Department of Molecular and Cell Biology and a Howard Hughes Medical Institute investigator.

They subsequently treated worms and human cells with Huntington’s disease with drugs that prevented the cell from sweeping up and storing the lipid, called ceramide, and saw the same protective effect.

“If we could manipulate this lipid pathway, we could go after Huntington’s disease, because in our studies the drugs were really beneficial,” he said. “This is poised to take to the next level.”

Dillin has already begun experiments in mice with Huntington’s disease to see if the drugs result in a better outcome. He will publish his latest findings online Sept. 8 in the journal Cell.

How Huntington’s disease causes wasting

In an accompanying paper in the same issue of Cell, Dillin also reports that stressing neurons in the brain makes them release a hormone, serotonin, that sends alert messages throughout the body that the brain cells are under attack, setting off a similar stress response in cells far from the brain. In diseases like Huntington’s, mental decline is also associated with peripheral metabolic defects and muscle decline.

“The serotonin release dramatically changes the metabolic output of peripheral cells and the sources they use for fuel, so we think it is instituting a large-scale metabolic rewiring, maybe to protect the neurons in the brain,” he said. “If you begin to shut down the periphery and stop using the limited resources it utilizes, then more of those resources can be shifted to brain metabolic activity. This might be a very clever way to try to save the brain by having the body waste away.”

While Dillin discovered the ability of mitochondria to communicate between different cells and tissues several years ago, the new study pinpoints serotonin as a primary driver of this metabolic response, he said.

Dillin noted that drugs that lower levels of serotonin have long been used to treat depression and other psychiatric manifestations of neurodegenerative diseases, but the new findings suggest these medications may have more widespread use in age-related disease than was previously thought. These findings have broad implications not only for the potential treatment of neurodegenerative disorders, but for further understanding the impact of neurological disease on metabolism and stress responses throughout the body.

Mitochondria key to brain degeneration

Both discoveries came from studies of mitochondria, the powerhouses of the cell that burn nutrients for energy but also play a key role in signaling, cell death and growth. Over the past several years, increasing evidence has associated mitochondrial dysfunctions with aging and age-onset protein misfolding diseases such as Alzheimer’s, Parkinson’s and Huntington’s.

Dillin is particularly interested in Huntington’s disease, which is inherited and strikes people in their 40s and 50s, inevitably leading to a wasting death. The genetic cause is well-known – expansion of a part of a gene that produces a protein with too many added glutamine amino acids. How this glutamine-rich protein leads to symptoms is only graduatlly being revealed.

While investigating mitochondria in nematodes genetically engineered to have Huntington’s disease, Dillin and his colleagues discovered that the abnormal proteins actually aggregate on the mitochondria, and that this ramps up the protein folding response within the cell, flooding both the mitochrondria and the cell interior with nearly 100 types of so-called heat shock proteins to try to fix the misfolded proteins. The heat-shock proteins act as mitochondrial chaperones to assist in the import and folding of mitochondrial proteins synthesized outside of mitochondria.

The researchers were surprised to find that knockdown of one specific mitochondrial chaperone, mtHSP70, elicited a unique stress response mediated by fat accumulation, resulting in improved protein folding in the interior or cytosol of the cell. Drugs that activate this novel stress response pathway, which they call the mitochondrial-to-cytosolic stress response, protected both nematodes and cultured human cells with Huntington´s disease from protein-folding damage.

“Maybe there is a way to use one drug to alter the mitochondrial signal and another drug to alter the communciation signal from the brain,” he said. “You would never see these two effects if you were studying protein folding in a tissue culture dish, because you don’t have the whole organism, C. elegans, in which you can look at the signals being communicated.”

ShareTweetSendScanShareSharePinSend

NEWSLETTER SIGN-UP

STAY CONNECTED

TRENDING

Study uncovers a “particularly alarming” link between men’s feelings of personal deprivation and hostile sexism

One in four people may experience estrangement from a sibling in adulthood, study finds

Virtual reality can inoculate people against the allure of alternative romantic partners, study finds

Two “dark” personality traits help explain the link between childhood adversity and suicide risk

Nipple erection influences perceptions of women’s intelligence, morality, and sexuality

Study links deviations in circadian rhythm patterns to psychiatric problems in adolescents

RECENT

Nipple erection influences perceptions of women’s intelligence, morality, and sexuality

When skin becomes smoother, the face is seen as prettier, even if it isn’t detectable

Study uncovers a “particularly alarming” link between men’s feelings of personal deprivation and hostile sexism

New study links “catfishing” to heightened levels of psychopathy, narcissism, and sadism

Many self-identified heterosexuals report feeling attracted toward individuals of the same sex, study finds

Two “dark” personality traits help explain the link between childhood adversity and suicide risk

People are more inclined to get COVID-19 booster after reading tweets that target regret, study finds

Study links deviations in circadian rhythm patterns to psychiatric problems in adolescents

Currently Playing

Individuals with dark personality traits are less oriented towards long-term mating strategies

Disclosing victim status reduces online dating matches regardless of race or sex

Individuals with dark personality traits are less oriented towards long-term mating strategies

Dark Triad
Longitudinal study examines the effects of adversity on wise reasoning

New study examines the psychological mechanisms underlying Solomon’s paradox

Social Psychology
Engaging in religious practice, even if you don’t believe, may increase your capacity to delay gratification

Engaging in religious practice, even if you don’t believe, may increase your capacity to delay gratification

Cognitive Science
New study sheds light on how three distinct types of first impressions predict subsequent dating outcomes

New study sheds light on how three distinct types of first impressions predict subsequent dating outcomes

Relationships and Sexual Health
A single, moderate dose of psilocybin reduces depressive symptoms for at least two weeks, controlled study finds

A single, moderate dose of psilocybin reduces depressive symptoms for at least two weeks, controlled study finds

Depression
Study identifies factors that influence the link between men’s body esteem and their ability to enjoy their sexuality

Study identifies factors that influence the link between men’s body esteem and their ability to enjoy their sexuality

Mental Health
  • Cognitive Science
  • COVID-19
  • Mental Health
  • Social Psychology
  • Drug Research
  • Conspiracy Theories
  • Meditation
  • Psychology of Religion
  • Aviation Psychology and Human Factors
  • Relationships and Sexual Health
  • Evolutionary Psychology
  • Neuroimaging
  • Psychedelic Drugs
  • Dark Triad
  • Political Psychology

About

PsyPost is a psychology and neuroscience news website dedicated to reporting the latest research on human behavior, cognition, and society. (READ MORE...)

  • Contact us
  • Privacy policy

Subscribe
  • My Account
  • Cognitive Science Research
  • Mental Health Research
  • Social Psychology Research
  • About PsyPost
    • Contact us
  • Privacy policy

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In

Add New Playlist

This website uses cookies. By continuing to use this website you are giving consent to cookies being used.