Neuroscience

Articles and news from the latest research reports.

Posts tagged neuroscience

160 notes

Research advances understanding of the human brain Advanced neuroimaging techniques are giving researchers new insight into how the human brain plans and controls limb movements. This advance could one day lead to new understanding of disease and dysfunction in the brain and has important implications for movement-impaired patient populations, like those who suffer from spinal cord injuries. Randy Flanagan (Psychology and Centre for Neuroscience Studies), working with colleagues at Western University, used functional magnetic resonance imaging (fMRI) to uncover what regions of the human brain are used to plan hand actions with the left and right arm. This study, spearheaded by Jason Gallivan, a Banting postdoctoral fellow at Queen’s found that by using the fMRI signals from several different brain regions, they could predict the limb to be used (left vs. right) and hand action to be performed (grasping vs. touching an object), moments before that movement is actually executed. “We are trying to understand how the brain plans actions,” says Dr. Gallivan. “By using highly sensitive analysis techniques that enable the detection of subtle changes in brain activity patterns, we can reveal which of a series of actions a volunteer is merely intending to do, seconds later. Mapping and characterizing these predictive signals across the human brain allows us to pinpoint the key brain structures involved in generating normal, everyday behaviours.” In another study, Dr. Flanagan and doctoral student Jonathan Diamond examined how the brain learns object mechanical properties, knowledge that is essential for skilled manipulation. They found that, through experience, humans use mismatches between predicted and actual fingertip forces and between predicted and actual object motions to build internal representations, or models, of the mechanical properties of the objects. “The goal of this work is to understand the representations underlying skilled manipulation,” explains Dr. Flanagan. “This is important because it will enable us to better characterize deficits in manipulation tasks that often result from stroke and neurological diseases.” Dr. Flanagan, Dr. Gallivan, and Ingrid Johnsrude (Psychology and Centre for Neuroscience Studies) have recently been awarded a CIHR operating grant to support ongoing neuroimaging work. Both research papers were published in the Journal of Neuroscience. Read Dr. Flanagan’s paper here and read the joint paper here. (Image: Getty Images)

Research advances understanding of the human brain

Advanced neuroimaging techniques are giving researchers new insight into how the human brain plans and controls limb movements. This advance could one day lead to new understanding of disease and dysfunction in the brain and has important implications for movement-impaired patient populations, like those who suffer from spinal cord injuries.

Randy Flanagan (Psychology and Centre for Neuroscience Studies), working with colleagues at Western University, used functional magnetic resonance imaging (fMRI) to uncover what regions of the human brain are used to plan hand actions with the left and right arm. This study, spearheaded by Jason Gallivan, a Banting postdoctoral fellow at Queen’s found that by using the fMRI signals from several different brain regions, they could predict the limb to be used (left vs. right) and hand action to be performed (grasping vs. touching an object), moments before that movement is actually executed.

“We are trying to understand how the brain plans actions,” says Dr. Gallivan. “By using highly sensitive analysis techniques that enable the detection of subtle changes in brain activity patterns, we can reveal which of a series of actions a volunteer is merely intending to do, seconds later. Mapping and characterizing these predictive signals across the human brain allows us to pinpoint the key brain structures involved in generating normal, everyday behaviours.”

In another study, Dr. Flanagan and doctoral student Jonathan Diamond examined how the brain learns object mechanical properties, knowledge that is essential for skilled manipulation. They found that, through experience, humans use mismatches between predicted and actual fingertip forces and between predicted and actual object motions to build internal representations, or models, of the mechanical properties of the objects.

“The goal of this work is to understand the representations underlying skilled manipulation,” explains Dr. Flanagan. “This is important because it will enable us to better characterize deficits in manipulation tasks that often result from stroke and neurological diseases.”

Dr. Flanagan, Dr. Gallivan, and Ingrid Johnsrude (Psychology and Centre for Neuroscience Studies) have recently been awarded a CIHR operating grant to support ongoing neuroimaging work.

Both research papers were published in the Journal of Neuroscience. Read Dr. Flanagan’s paper here and read the joint paper here.

(Image: Getty Images)

Filed under brain spinal cord injuries neuroimaging brain activity limb movements neuroscience science

74 notes

Scientists Identify ‘Clean-Up’ Snafu That Kills Brain Cells in Parkinson’s Disease Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the most common genetic mutations in familial Parkinson’s disease damage brain cells. The study, which published online in the journal Nature Neuroscience, could also open up treatment possibilities for both familial Parkinson’s and the more common form of Parkinson’s that is not inherited. "Our study found that abnormal forms of LRRK2 protein disrupt an important garbage-disposal process in cells that normally digests and recycles unwanted proteins including one called alpha-synuclein - the main component of those protein aggregates that gunk up nerve cells in Parkinson’s patients," said study leader Ana Maria Cuervo, M.D., Ph.D., professor of  developmental and molecular biology, of anatomy and structural biology, and of medicine and the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein. The name for the disrupted disposal process is chaperone-mediated autophagy (the word “autophagy” literally means “self-eating”). It involves specialized molecules that “guide” old and damaged proteins to enzyme-filled structures called lysosomes; there the proteins are digested into amino acids, which are then recycled within the cell. "We showed that when LRRK2 inhibits chaperone-mediated autophagy,alpha-synuclein doesn’t get broken down and instead accumulates to toxic levels in nerve cells,” said Dr. Cuervo. The study involved mouse neurons in tissue culture from four different animal models, neurons from the brains of patients with Parkinson’s with  LRRK2 mutations, and neurons derived from the skin cells of Parkinson’s patients via induced pluripotent stem (iPS) cell technology. All the lines of research confirmed the researchers’ discovery. "We’re now looking at ways to enhance the activity of this recycling system to see if we can prevent or delay neuronal death and disease," said Dr. Cuervo. "We’ve started to analyze some chemical compounds that look very promising." Dr. Cuervo hopes that such treatments could help patients with familial as well as nonfamilial Parkinson’s - the predominant form of the disease that also involves the buildup of alpha-synuclein. Dr. Cuervo is credited with discovering chaperone-mediated autophagy. She has published extensively on autophagy and its role in numerous diseases, such as cancer and Huntington’s disease, and its role in age-related conditions, including organ decline and weakened immunity. Dr. Cuervo is co-director of Einstein’s  Institute of Aging Research. (Image: Shutterstock)

Scientists Identify ‘Clean-Up’ Snafu That Kills Brain Cells in Parkinson’s Disease

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the most common genetic mutations in familial Parkinson’s disease damage brain cells. The study, which published online in the journal Nature Neuroscience, could also open up treatment possibilities for both familial Parkinson’s and the more common form of Parkinson’s that is not inherited.

"Our study found that abnormal forms of LRRK2 protein disrupt an important garbage-disposal process in cells that normally digests and recycles unwanted proteins including one called alpha-synuclein - the main component of those protein aggregates that gunk up nerve cells in Parkinson’s patients," said study leader Ana Maria Cuervo, M.D., Ph.D., professor of  developmental and molecular biology, of anatomy and structural biology, and of medicine and the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein.

The name for the disrupted disposal process is chaperone-mediated autophagy (the word “autophagy” literally means “self-eating”). It involves specialized molecules that “guide” old and damaged proteins to enzyme-filled structures called lysosomes; there the proteins are digested into amino acids, which are then recycled within the cell.

"We showed that when LRRK2 inhibits chaperone-mediated autophagy,
alpha-synuclein doesn’t get broken down and instead accumulates to toxic levels in nerve cells,” said Dr. Cuervo.

The study involved mouse neurons in tissue culture from four different animal models, neurons from the brains of patients with Parkinson’s with  LRRK2 mutations, and neurons derived from the skin cells of Parkinson’s patients via induced pluripotent stem (iPS) cell technology. All the lines of research confirmed the researchers’ discovery.

"We’re now looking at ways to enhance the activity of this recycling system to see if we can prevent or delay neuronal death and disease," said Dr. Cuervo. "We’ve started to analyze some chemical compounds that look very promising."

Dr. Cuervo hopes that such treatments could help patients with familial as well as nonfamilial Parkinson’s - the predominant form of the disease that also involves the buildup of alpha-synuclein.

Dr. Cuervo is credited with discovering chaperone-mediated autophagy. She has published extensively on autophagy and its role in numerous diseases, such as cancer and Huntington’s disease, and its role in age-related conditions, including organ decline and weakened immunity. Dr. Cuervo is co-director of Einstein’s  Institute of Aging Research.

(Image: Shutterstock)

Filed under neurodegenerative diseases parkinson's disease autophagy nerve cells proteins neuroscience science

96 notes

“Seq-ing” Insights into the Epigenetics of Neuronal Gene Regulation The epigenetic control of neuronal gene expression patterns has emerged as an underlying regulatory mechanism for neuronal function, identity, and plasticity, in which short- to long-lasting adaptation is required to dynamically respond and process external stimuli. To achieve a comprehensive understanding of the physiology and pathology of the brain, it becomes essential to understand the mechanisms that regulate the epigenome and transcriptome in neurons. Here, we review recent advances in the study of regulated neuronal gene expression, which are dramatically expanding as a result of the development of new and powerful contemporary methodologies, based on next-generation sequencing. This flood of new information has already transformed our understanding of many biological processes and is now driving discoveries elucidating the molecular mechanisms of brain function in cognition, behavior, and disease and may also inform the study of neuronal identity, diversity, and neuronal reprogramming.

“Seq-ing” Insights into the Epigenetics of Neuronal Gene Regulation

The epigenetic control of neuronal gene expression patterns has emerged as an underlying regulatory mechanism for neuronal function, identity, and plasticity, in which short- to long-lasting adaptation is required to dynamically respond and process external stimuli. To achieve a comprehensive understanding of the physiology and pathology of the brain, it becomes essential to understand the mechanisms that regulate the epigenome and transcriptome in neurons. Here, we review recent advances in the study of regulated neuronal gene expression, which are dramatically expanding as a result of the development of new and powerful contemporary methodologies, based on next-generation sequencing. This flood of new information has already transformed our understanding of many biological processes and is now driving discoveries elucidating the molecular mechanisms of brain function in cognition, behavior, and disease and may also inform the study of neuronal identity, diversity, and neuronal reprogramming.

Filed under epigenetics gene expression deep sequencing neurons neuronal function brain development genetics neuroscience science

262 notes

Reconstructing the Past: How Recalling Memories Alters Them Recently the neurologist and author Oliver Sacks recalled a vivid childhood memory, recounted in his autobiography, Uncle Tungsten. During WWII he lived in London during the Blitz, and on one occasion: "…an incendiary bomb, a thermite bomb, fell behind our house and burned with a terrible, white-hot heat. My father had a stirrup pump, and my brothers carried pails of water to him, but water seemed useless against this infernal fire—indeed, made it burn even more furiously. There was a vicious hissing and sputtering when the water hit the white-hot metal, and meanwhile the bomb was melting its own casing and throwing blobs and jets of molten metal in all directions." Except when his autobiography came out, one of his older brothers told him he’d misremembered the event. In fact both of them had been at school when the bomb struck so they could not have witnessed the explosion. The ‘false’ memory, it turned out, was implanted by a letter. Their elder brother had written to them, describing the frightening event, and this had lodged in his mind. Over the years the letter had gone from a third-person report to a first-person ‘memory’. Turning the memory over in his mind, Sacks writes that he still cannot see how the memory of the bomb exploding can be false. There is no difference between this memory and others he knows to be true; it felt like he was really there. This sort of experience is probably much more common than we might like to imagine. Many memories which have the scent of authenticity may turn out to be misremembered, if not totally fictitious events, if only we could check. Without some other source with which to corroborate, it is hard verify the facts, especially for events that took place long ago. That these sorts of distortions to memory happen is unquestioned, what fascinates is how it comes about. Does the long passage of time warp the memory, or is there some more active process that causes the change? A study published recently sheds some light on this process and provides a model for how memories like Sack’s become distorted.

Reconstructing the Past: How Recalling Memories Alters Them

Recently the neurologist and author Oliver Sacks recalled a vivid childhood memory, recounted in his autobiography, Uncle Tungsten.

During WWII he lived in London during the Blitz, and on one occasion:

"…an incendiary bomb, a thermite bomb, fell behind our house and burned with a terrible, white-hot heat. My father had a stirrup pump, and my brothers carried pails of water to him, but water seemed useless against this infernal fire—indeed, made it burn even more furiously. There was a vicious hissing and sputtering when the water hit the white-hot metal, and meanwhile the bomb was melting its own casing and throwing blobs and jets of molten metal in all directions."

Except when his autobiography came out, one of his older brothers told him he’d misremembered the event. In fact both of them had been at school when the bomb struck so they could not have witnessed the explosion.

The ‘false’ memory, it turned out, was implanted by a letter. Their elder brother had written to them, describing the frightening event, and this had lodged in his mind. Over the years the letter had gone from a third-person report to a first-person ‘memory’.

Turning the memory over in his mind, Sacks writes that he still cannot see how the memory of the bomb exploding can be false. There is no difference between this memory and others he knows to be true; it felt like he was really there.

This sort of experience is probably much more common than we might like to imagine. Many memories which have the scent of authenticity may turn out to be misremembered, if not totally fictitious events, if only we could check. Without some other source with which to corroborate, it is hard verify the facts, especially for events that took place long ago.

That these sorts of distortions to memory happen is unquestioned, what fascinates is how it comes about. Does the long passage of time warp the memory, or is there some more active process that causes the change?

A study published recently sheds some light on this process and provides a model for how memories like Sack’s become distorted.

Filed under memory false memory episodic memory autobiographical memory psychology neuroscience science

104 notes

Every science writer loves a good challenge to dogma. I wish I had been in the working world in the spring of 1992, when one such intellectual overhaul happened in neuroscience. The dogma: Neurons, unlike most of the body’s cells, can’t be replenished. You’re born with just 100 billion of them and you better use them wisely. The challenge: Samuel Weiss and Brent Reynolds reported in Science that brain tissue taken from adult mice could be chemically coaxed into making new neurons. “It left us speechless,” Weiss told the New York Times. Everybody else was pretty stunned, too. Over the next six years, other researchers confirmed that this so-called neurogenesis happens in the adult hippocampus of many animals, including tree shrews, marmosets, Old World monkeys and people. Today, more than two decades since the splashy Science report, adult neurogenesis is a bona fide subfield, with hundreds of labs studying it around the world. But after all this time, researchers still don’t really know what it’s for. Studies have uncovered a wide variety of environmental stimuli — what you might think of as inputs — that affect neurogenesis in the dentate gyrus, a part of the hippocampus. Running and antidepressants can ramp up neurogenesis, for example, while stress, social isolation, sleep deprivation and aging can shut it down. Scientists have also looked at the outputs of neurogenesis, showing that a boost of new neurons may be important for exploratory behavior and certain kinds of learning, such as navigating a new space. But how do the inputs lead to the outputs? “I like to think of the dentate as an association machine,” says Sam Pleasure, a neuroscientist at the University of California, San Francisco. All day long, he says, we’re walking around the world trying to associate various sensations and emotions — big dog with fangs, small screaming toddler, perilous traffic intersection — so that we can remember them later. “All these stimuli are happening and converge on this circuit, and they somehow affect how new neurons are recruited into the circuit, and that ends up coming out as the ability to form new memories.” But how it all works on the molecular level is a black box. Two papers published in Cell Stem Cell [1 , 2]open that box a little bit. They identify molecular inhibitors — what Pleasure calls “wet blankets” — that turn off neurogenesis in certain contexts. Opening the Black Box of Neurogenesis by Virginia Hughes

Every science writer loves a good challenge to dogma. I wish I had been in the working world in the spring of 1992, when one such intellectual overhaul happened in neuroscience. The dogma: Neurons, unlike most of the body’s cells, can’t be replenished. You’re born with just 100 billion of them and you better use them wisely. The challenge: Samuel Weiss and Brent Reynolds reported in Science that brain tissue taken from adult mice could be chemically coaxed into making new neurons.

“It left us speechless,” Weiss told the New York Times. Everybody else was pretty stunned, too. Over the next six years, other researchers confirmed that this so-called neurogenesis happens in the adult hippocampus of many animals, including tree shrews, marmosets, Old World monkeys and people. Today, more than two decades since the splashy Science report, adult neurogenesis is a bona fide subfield, with hundreds of labs studying it around the world.

But after all this time, researchers still don’t really know what it’s for. Studies have uncovered a wide variety of environmental stimuli — what you might think of as inputs — that affect neurogenesis in the dentate gyrus, a part of the hippocampus. Running and antidepressants can ramp up neurogenesis, for example, while stress, social isolation, sleep deprivation and aging can shut it down. Scientists have also looked at the outputs of neurogenesis, showing that a boost of new neurons may be important for exploratory behavior and certain kinds of learning, such as navigating a new space. But how do the inputs lead to the outputs?

“I like to think of the dentate as an association machine,” says Sam Pleasure, a neuroscientist at the University of California, San Francisco. All day long, he says, we’re walking around the world trying to associate various sensations and emotions — big dog with fangs, small screaming toddler, perilous traffic intersection — so that we can remember them later. “All these stimuli are happening and converge on this circuit, and they somehow affect how new neurons are recruited into the circuit, and that ends up coming out as the ability to form new memories.” But how it all works on the molecular level is a black box.

Two papers published in Cell Stem Cell [1 , 2]open that box a little bit. They identify molecular inhibitors — what Pleasure calls “wet blankets” — that turn off neurogenesis in certain contexts.

Opening the Black Box of Neurogenesis by Virginia Hughes

Filed under neurons neurogenesis hippocampus dentate gyrus neuroscience science

123 notes

Changes in patterns of brain activity predict fear memory formation Psychologists at the University of Amsterdam (UvA) have discovered that changes in patterns of brain activity during fearful experiences predict whether a long-term fear memory is formed. The research results have recently been published in the prestigious scientific journal ‘Nature Neuroscience’. Researchers Renee Visser MSc, Dr Steven Scholte, Tinka Beemsterboer MSc and Prof. Merel Kindt discovered that they can predict future fear memories by looking at patterns of brain activity during fearful experiences. Up until now, there was no way of predicting fear memory. It was also, above all, unclear whether the selection of information to be stored in the long-term memory occurred at the time of fear learning or after the event. Picture predicts pain stimulus During magnetic resonance brain imaging (MRI), participants saw neutral pictures of faces and houses, some of which were followed by a small electric shock. In this way, the participants formed fear memories. They showed fear responses when the pictures were shown that were paired with shocks. This fear response can be measured in the brain, but is also evident from increased pupil dilation when someone sees the picture. After a few weeks, the participants returned to the lab and were shown the same images. Brain activity and pupil diameter were once again measured. The extent to which the pupil dilated when seeing the images that were previously followed by a shock, was considered an expression of the previously formed fear memory. Pattern Analysis In order to analyse the fMRI data, (spatial) patterns of brain activity (Multi-Voxel Pattern Analysis, or MVPA) were analysed. By correlating patterns of various stimulus presentations with each other, it is possible to measure the extent to which the representation of two stimuli is the same. It appears that images that have nothing in common, such as houses and faces, lead to increasing neural pattern similarity when they predict danger. This does not occur when they do not predict danger. This leads to the formation of stronger fear responses. The extent to which this occurs is an indication of fear memory formation: the stronger the response during learning, the stronger the fear response will be in the long term. These findings may lead to greater insights into the formation of emotional memory. As a result, it is possible to conduct experimental research into the mechanisms that strengthen, weaken or even erase fear memory in a more direct fashion, without having to wait until the fear memory is expressed.

Changes in patterns of brain activity predict fear memory formation

Psychologists at the University of Amsterdam (UvA) have discovered that changes in patterns of brain activity during fearful experiences predict whether a long-term fear memory is formed. The research results have recently been published in the prestigious scientific journal ‘Nature Neuroscience’.

Researchers Renee Visser MSc, Dr Steven Scholte, Tinka Beemsterboer MSc and Prof. Merel Kindt discovered that they can predict future fear memories by looking at patterns of brain activity during fearful experiences. Up until now, there was no way of predicting fear memory. It was also, above all, unclear whether the selection of information to be stored in the long-term memory occurred at the time of fear learning or after the event.

Picture predicts pain stimulus

During magnetic resonance brain imaging (MRI), participants saw neutral pictures of faces and houses, some of which were followed by a small electric shock. In this way, the participants formed fear memories. They showed fear responses when the pictures were shown that were paired with shocks. This fear response can be measured in the brain, but is also evident from increased pupil dilation when someone sees the picture. After a few weeks, the participants returned to the lab and were shown the same images. Brain activity and pupil diameter were once again measured. The extent to which the pupil dilated when seeing the images that were previously followed by a shock, was considered an expression of the previously formed fear memory.

Pattern Analysis

In order to analyse the fMRI data, (spatial) patterns of brain activity (Multi-Voxel Pattern Analysis, or MVPA) were analysed. By correlating patterns of various stimulus presentations with each other, it is possible to measure the extent to which the representation of two stimuli is the same. It appears that images that have nothing in common, such as houses and faces, lead to increasing neural pattern similarity when they predict danger. This does not occur when they do not predict danger. This leads to the formation of stronger fear responses. The extent to which this occurs is an indication of fear memory formation: the stronger the response during learning, the stronger the fear response will be in the long term.

These findings may lead to greater insights into the formation of emotional memory. As a result, it is possible to conduct experimental research into the mechanisms that strengthen, weaken or even erase fear memory in a more direct fashion, without having to wait until the fear memory is expressed.

Filed under brain activity fear memory memory formation fear memory psychology neuroscience science

59 notes

Misplaced molecules: New insights into the causes of dementia

A shortage of a protein called TDP-43 caused muscle wasting and stunted nerve cells. This finding supports the idea that malfunction of this protein plays a decisive role in ALS and FTD. The study is published in the “Proceedings of the National Academy of Sciences of the USA" (PNAS).

ALS is an incurable neurological disease which manifests as rapidly progressing muscle wasting. Both limbs and respiratory muscles are affected. This leads to impaired mobility and breathing problems. Patients commonly die within a few years after the symptoms emerged. In rare cases, of which the British physicist Stephen Hawking is the most notable, patients can live with the disease for a long time. In Germany estimates show over 150,000 patients suffering from ALS – an average of 1 in 500 people.

Proteins gone astray

Over the last few years, there has been increasing evidence that ALS and FTD – a form of dementia associated with changes in personality and social behaviour – may have similar or even the same origins. The symptoms overlap and common factors have also been found at the microscopic level. In many cases, particles accumulate and form clumps in the patient’s nerve cells: this applies particularly to the TDP-43 protein.

"Normally, this protein is located in the cell nucleus and is involved in processing genetic information," explains molecular biologist Dr. Bettina Schmid, who works at the DZNE Munich site and at LMU. "However, in cases of disease, TDP-43 accumulates outside the nucleus forming aggregates." Schmid explains that it is not yet clear whether these clumps are harmful. "However, the protein’s normal function is clearly disrupted. It no longer reaches the nucleus to perform its actual task. There seems to be a relationship between this malfunction and the disease."

Studies on zebrafish

However, until now little was known about the function of TDP-43. What are the consequences when this protein becomes non-functional? In order to answer this question, the team led by Bettina Schmid cooperated with the research group of Prof. Christian Haass to investigate the larvae of specially bred zebrafish. Their genetic code had been modified in such a way that no TDP-43 was produced in the organism of the fish. The result: the young fish showed massive muscle wasting and died a few days after hatching. Moreover, the extensions of the nerve cells which control the muscles were abnormal.

"To some extent, these are symptoms typical of ALS and FTD. Therefore, a loss of function of TDP-43 does seem to play a critical role in the disease," says Haass, Site Speaker of the DZNE Munich Site and chair of Metabolic Biochemistry at LMU.

The study revealed one more finding which surprised the researchers: the blood flow of the fish was massively disturbed. “It is well known that circulatory disorders play a part in other forms of dementia, notably in the case of Alzheimer’s,” says Haass. “We now want to investigate whether such problems with blood flow may be a general problem of neurodegenerative diseases and whether such problems occur particularly in patients with ALS and FTD.”

(Source: eurekalert.org)

Filed under neurodegenerative diseases dementia nerve cells proteins zebrafish ALS blood flow neuroscience science

53 notes

Parkin protects from neuronal cell death Parkinson’s disease is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer’s disease. It is characterized by the loss of dopamin-producing neurons in the substantia nigra, a region in the midbrain, which is implicated in motor control. The typical clinical signs include resting tremor, muscle rigidity, slowness of movements, and impaired balance. In about 10% of cases Parkinson’s disease is caused by mutations in specific genes, one of them is called parkin. “Parkinson-associated genes are particularly interesting for researchers, since insights into the function and dysfunction of these genes allow conclusions on the pathomechanisms underlying Parkinson’s disease”, says Dr. Konstanze Winklhofer of the Adolf Butenandt Institute at the LMU Munich, who is also affiliated with the German Center for Neurodegenerative Diseases (DZNE). Winklhofer and her colleagues had previously observed that parkin can protect neurons from cell death under various stress conditions. In the course of this project, it became obvious that a loss of parkin function impairs the activity and integrity of mitochondria, which serve as the cellular power stations. In their latest publication, Winklhofer and coworkers uncovered the molecular mechanism that accounts for parkin’s neuroprotective action. “We discovered a novel signaling pathway that is responsible for the neuroprotective activity of parkin,” Winklhofer reports. The central player of this pathway is a protein called NEMO, which is activated by the enzymatic attachment of a linear chain of ubiquitin molecules. This reaction is promoted by parkin, thereby enabling NEMO to activate a signal cascade, which ultimately leads to the expression of a specific set of genes. Winklhofer’s team identified one essential gene targeted by this pathway, which turned out to code for the mitochondrial protein OPA1. OPA1 maintains the integrity of mitochondria and prevents stress-induced neuronal cell death. “These findings suggest that strategies to activate this signal pathway or to enhance the synthesis of OPA1 in cells exposed to stress could be of therapeutic benefit,” Winklhofer points out. The newly identified signal pathway may also be relevant in the context of other neurological conditions that are characterized by the loss of specific neurons. Konstanze Winklhofer and her group are already engaged in further projects designed to determine whether other molecules regulated by this pathway might provide targets for therapeutic interventions.

Parkin protects from neuronal cell death

Parkinson’s disease is the most common movement disorder and the second most common neurodegenerative disease after Alzheimer’s disease. It is characterized by the loss of dopamin-producing neurons in the substantia nigra, a region in the midbrain, which is implicated in motor control. The typical clinical signs include resting tremor, muscle rigidity, slowness of movements, and impaired balance. In about 10% of cases Parkinson’s disease is caused by mutations in specific genes, one of them is called parkin.

“Parkinson-associated genes are particularly interesting for researchers, since insights into the function and dysfunction of these genes allow conclusions on the pathomechanisms underlying Parkinson’s disease”, says Dr. Konstanze Winklhofer of the Adolf Butenandt Institute at the LMU Munich, who is also affiliated with the German Center for Neurodegenerative Diseases (DZNE). Winklhofer and her colleagues had previously observed that parkin can protect neurons from cell death under various stress conditions. In the course of this project, it became obvious that a loss of parkin function impairs the activity and integrity of mitochondria, which serve as the cellular power stations. In their latest publication, Winklhofer and coworkers uncovered the molecular mechanism that accounts for parkin’s neuroprotective action.

“We discovered a novel signaling pathway that is responsible for the neuroprotective activity of parkin,” Winklhofer reports. The central player of this pathway is a protein called NEMO, which is activated by the enzymatic attachment of a linear chain of ubiquitin molecules. This reaction is promoted by parkin, thereby enabling NEMO to activate a signal cascade, which ultimately leads to the expression of a specific set of genes. Winklhofer’s team identified one essential gene targeted by this pathway, which turned out to code for the mitochondrial protein OPA1. OPA1 maintains the integrity of mitochondria and prevents stress-induced neuronal cell death.

“These findings suggest that strategies to activate this signal pathway or to enhance the synthesis of OPA1 in cells exposed to stress could be of therapeutic benefit,” Winklhofer points out.

The newly identified signal pathway may also be relevant in the context of other neurological conditions that are characterized by the loss of specific neurons. Konstanze Winklhofer and her group are already engaged in further projects designed to determine whether other molecules regulated by this pathway might provide targets for therapeutic interventions.

Filed under parkinson's disease parkin cell death mitochondria proteins neurons neuroscience science

free counters