Posts tagged neurodegenerative diseases
Articles and news from the latest research reports.
How a small worm may help the fight against Alzheimer’s
Scientists at the Max Planck Institute for Biology of Ageing in Cologne have found that a naturally occurring molecule has the ability to enhance defense mechanisms against neurodegenerative diseases. Feeding this particular metabolite to the small round worm Caenorhabditis elegans, helps clear toxic protein aggregates in the body and extends life span.
During ageing, proteins in the human body tend to aggregate. At a certain point, protein aggregation becomes toxic, overloads the cell, and thus prevents it from maintaining normal function. Damage can occur, particularly in neurons, and may result in neurodegenerative diseases like Alzheimer’s, Parkinson’s or Huntington’s disease. By studying model organisms like Caenorhabditis elegans, scientists have begun to uncover the mechanisms underlying neurodegeneration, and thus define possible targets for both therapy and prevention of those diseases. “Although we cannot measure dementia in worms“, explains Martin Denzel of the Max Planck Institute for Biology of Ageing, “we can observe proteins that we also know from human diseases like Alzheimer’s to be toxic by measuring effects on neuromuscular function. This gives us insight into how Alzheimer actually progresses on the molecular level“.
Now, the scientists Martin Denzel, Nadia Storm, and Max Planck Director Adam Antebi have discovered that a substance called N-acetylglucosamine apparently stimulates the body’s own defense mechanism against such toxicity. This metabolite occurs naturally in the organism. If it is additionally fed to the worm, “we can achieve very dramatic benefits“, says Denzel. “It is a broad-spectrum effect that alleviates protein toxicity in Alzheimer’s, Parkinson’s and Huntington’s disease models in the worm, and it even extends their life span.“
This molecule apparently plays a crucial role in quality control mechanisms that keep the body healthy. It helps the organism to clear toxic levels of protein aggregation, both preventing aggregates from forming and clearing already existing ones. As a result, onset of paralysis is delayed in models of neurodegeneration - How exactly the molecule achieves this effect is yet to be uncovered. “And we still don’t know whether it also works in higher animals and humans“, says Antebi. “But as we also have these metabolites in our cells, this gives good reason to suspect that similar mechanisms might work in humans.”
Scientists catch brain damage in the act
Scientists have uncovered how inflammation and lack of oxygen conspire to cause brain damage in conditions such as stroke and Alzheimer’s disease.
The discovery, published today in Neuron, brings researchers a step closer to finding potential targets to treat neurodegenerative disorders.
Chronic inflammation and hypoxia, or oxygen deficiency, are hallmarks of several brain diseases, but little was known about how they contribute to symptoms such as memory loss.
The study used state-of-the-art techniques that reveal the movements of microglia, the brain’s resident immune cells. Brain researcher Brian MacVicar had previously captured how they moved to areas of injury to repair brain damage.
The new study shows that the combination of inflammation and hypoxia activates microglia in a way that persistently weakens the connection between neurons. The phenomenon, known as long-term depression, has been shown to contribute to cognitive impairment in Alzheimer’s disease.
“This is a never-before-seen mechanism among three key players in the brain that interact together in neurodegenerative disorders,” says MacVicar with the Djavad Mowafaghian Centre for Brain Health at UBC and Vancouver Coastal Health Research Institute.
“Now we can use this knowledge to start identifying new potential targets for therapy.”
New risk gene illuminates Alzheimer’s disease
A team of international scientists, including a researcher from Simon Fraser University, has isolated a gene thought to play a causal role in the development of Alzheimer’s disease. The Proceedings of the National Academy of Sciences recently published the team’s study.
The newly identified gene affects accumulation of amyloid-beta, a protein believed to be one of the main causes of the damage that underpins this brain disease in humans.
The gene encodes a protein that is important for intracellular transportation. Each brain cell relies on an internal highway system that transports molecular signals needed for the development, communication, and survival of the cell.
This system’s impairment can disrupt amyloid-beta processing, causing its eventual accumulation. This contributes to the development of amyloid plaques, which are a key hallmark of Alzheimer’s disease.
Teasing out contributing disease factors, whether genetic or environmental, has long posed a challenge for Alzheimer’s researchers.
“Alzheimer’s is a multifactorial disease where a build-up of subtle problems develop in the nervous system over a span of decades,” says Michael Silverman, an SFU biology associate professor. He worked on the study with a team of Japanese scientists led by Dr. Takashi Morihara at Osaka University.
Identifying these subtle, yet perhaps critical genetic contributions is challenging. “Alzheimer’s, like many human disorders, has a genetic component, yet many environmental and lifestyle factors contribute to the disease as well,” says Silverman. “In a sense, it is like looking for a needle in a complex genetic haystack.”
Only a small fraction of cases have a strong hereditary component, for example early-onset Alzheimer’s.
This breakthrough in Alzheimer’s research could open new avenues for the design of therapeutics and pave the way for early detection by helping healthcare professionals identify those who are predisposed to the disease.
“One possibility is that a genetic test for a particular variant of this newly discovered gene, along with other variants of genes that contribute to Alzheimer’s, will help to give a person their overall risk for the disease.
“Lifestyle changes, such as improved diet, exercise, and an increase in cognitive stimulation may then help to slow the progression of Alzheimer’s,” says Silverman.
(Source: sfu.ca)
Environmentally sensitive cells with a Hulk-like rage
Human exposure to urban air pollution may trigger toxic responses in brain cells and impact neurodegenerative disease pathways
From diesel exhaust to gaseous pollutants and suspended particulate matter, such as dust, smoke and fumes, air pollution from transportation, industry and energy generation has taken a toll on the environment and human health.
While the adverse effects of air pollution on the cardiovascular and respiratory systems have been well documented, little is known about how the associated toxins may impact the brain and the central nervous system. In recent years, experts have reported a marked rise in the prevalence of stroke, autism and cognitive decline in the elderly.
Researchers such as Michelle Block, Ph.D., associate professor in the Department of Anatomy and Neurobiology in the Virginia Commonwealth University School of Medicine, are now on a mission to define the impact of air pollution on the brain and central nervous system.
Through basic science, Block and her team are working to understand the underlying molecular mechanisms in hopes of developing an intervention that can protect human health.
Recent scientific reports suggest air pollution exposure and the activation of a specific group of cells found in the brain being studied in Block’s laboratory may play a role in the increased incidence of central nervous system diseases and neurological conditions. They have observed that these factors may also impact the neurodegenerative disease process.
Last week, Block, presented her team’s significant research findings to peers from across the country during a symposium she co-organized at the 2014 annual meeting of the American Association for the Advancement of Science, held in Chicago, from Feb. 13 to 17.
“Angry” cells, toxic responses
Block’s research examines microglia, a group of resident immune cells found in the brain and spinal cord, which can display a kind of dual personality – one good, and the other bad if agitated.
Under normal conditions, microglia primarily serve as the defenders of the central nervous system. They bring balance to the system. They destroy infectious agents, engulf various unwanted cellular and foreign materials and promote regrowth of damaged neural tissue.
But microglia can be dangerous when they are exceptionally “angry” and are known to leave behind significant bystander damage to neighboring cells. This adverse behavior may lead to the development of any number of neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, or Gulf War Illness.
In some ways, microglia are similar to misunderstood superhero The Incredible Hulk. Despite having a decent-sized heart and extraordinary abilities to help save the day, nobody wants to stir his rage and anger.
Block’s laboratory specializes in understanding the cellular and molecular machinery responsible for essentially fueling microglia “anger” – why they become chronically and excessively activated to drive damage in the brain.
“Our goal is to define how microglia detect and respond to air pollution, reveal when this microglial response may actually be damaging the brain, identify potential markers of ongoing silent neuropathology and ultimately use the mechanistic information we acquire as a tool to halt the induced or augmented neuropathology,” Block said.
In several peer-reviewed, published reports, Block and her colleagues have demonstrated that exposure to a diverse source of urban air pollution can trigger toxic microglial responses and impact neurodegenerative disease pathways.
“Given the prevalence of human exposure to urban air pollution above safety regulations, it is critical to understand the underlying mechanisms through which air pollution affects the brain,” Block said. “We hope to find an opportunity to intervene and protect human central nervous system health.”
According to Block, her team’s work shows that many components of urban air pollution, including the particle components of air pollution, also called particulate matter, and gases, such as ground level ozone, activate microglia.
Some of the problems with this cell type come in when the same molecular tools used by microglia internalize (eat) and clean up toxic stimuli and accidentally trigger the switch to an excessive, angry activation state. The work she presented reveals how air pollution does this, essentially leaving microglia with much more than a mouthful. Her lab has discovered that the MAC1 pattern recognition receptor may be a common mechanism through which microglia detect and ultimately misinterpret different forms of air pollution as an invading pathogen to result in excessive production of reactive oxygen species and consequent damage to neighboring brain cells.
Further, ongoing research in Block’s lab aims to define where damage to the lungs through inhaled toxicants produces injury signals in the circulation that are not only detected by microglia in the brain, but are responsible for shifting microglia to a deleterious phenotype impacting central nervous system health. She refers to this as a “Lung-Brain Axis.”
Can a virtual brain replace lab rats?
Testing the effects of drugs on a simulated brain could lead to breakthrough treatments for neurological disorders such as Parkinson’s, Huntington’s and Alzheimer’s disease.
Researchers from the University of Waterloo in Canada hope Spaun, the world’s largest functioning model of the brain, will be used to test new drugs that lead to medical breakthroughs for brain disorders.
Terrence Stewart, a post-doctoral researcher with the Centre for Theoretical Neuroscience at Waterloo and project manager for Spaun, will tell an audience at the American Association for the Advancement of Science (AAAS) annual meeting in Chicago about the advantages of using whole-brain simulation as a tool to aid new discoveries in medicine.
“Our hope is that you could try out different possible treatments quickly to see how the brain reacts and how each one changes behaviour before testing them in people,” said Stewart. “Our brain model offers a new way to test treatments. For Alzheimer’s disease or a stroke that causes memory loss, we could see how a new drug affects the firing pattern of individual brain cells and measure how it changes brain performance on memory tests before trying it on people.”
Stewart’s team has already made progress simulating Parkinson’s and Huntington’s diseases. Their next step is to simulate Alzheimer’s disease after giving Spaun a hippocampus, the brain region involved in forming new memories.
Spaun is more like the human brain than other computer brain models because it makes mistakes and loses abilities in similar ways to people. To simulate the cognitive decline associated with aging, for example, Stewart and his team killed off neurons in the brain model and observed it gradually forgetting more numbers on a memory test.
To reproduce movement problems associated with Huntington’s disease and damage to the cerebellum, Stewart damaged parts of the simulated brain affected by those conditions.
“We showed that errors made in reaching behaviour seen in people with those disorders correspond to the errors made by our brain model when neurons in the affected brain regions are damaged,” he said.
Spaun can see, remember, think and write using a mechanical arm. Most importantly, this virtual brain – which mimics the neuron firing patterns seen in the human brain – allows the researchers to study and understand how damage to individual cells affects the behaviour of the whole brain in different neurological diseases.
Stewart presented new research on successfully simulating the effects of aging and Huntington’s disease in Spaun at a symposium panel, “Virtual Humans: Helping Facilitate Breakthroughs in Medicine” on Friday, February 14, 2014.
Huntington disease prevention trial shows creatine safe, suggests slowing of progression
The first clinical trial of a drug intended to delay the onset of symptoms of Huntington disease (HD) reveals that high-dose treatment with the nutritional supplement creatine was safe and well tolerated by most study participants. In addition, neuroimaging showed a treatment-associated slowing of regional brain atrophy, evidence that creatine might slow the progression of presymptomatic HD. The Massachusetts General Hospital (MGH) study also utilized a novel design that allowed participants – all of whom were at genetic risk for the neurodegenerative disorder – to enroll without having to learn whether or not they carried the mutation that causes HD.
"More than 90 percent of those in the United States who know they are at risk for HD because of their family history have abstained from genetic testing, often because they fear discrimination or don’t want to face the stress and anxiety of knowing they are destined to develop such a devastating disease," says H. Diana Rosas, MD, of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND), lead and corresponding author of the paper that will appear in the March 11 issue of Neurology and has been released online. “Many of these individuals would still like to help find treatments, and this trial design allows them to participate while respecting their autonomy, their right not to know their personal genetic information.”
Among the ways that the mutated form of the huntingtin protein damages brain cells is by interfering with cellular energy production, leading to a depletion of ATP, the molecule that powers most biological processes. Known to help restore ATP and maintain cellular energy, creatine is being investigated to treat a number of neurological conditions – including Parkinson disease, amyotrophic lateral sclerosis and spinal cord injury. Studies in mouse models of HD showed that creatine raises brain ATP levels and protects against neurodegeneration. Previous clinical trials of creatine in symptomatic HD patients have been limited in scale, involved daily doses of 10 grams or less, and did not provide evidence of potential efficacy. Based on the results of a pilot study at MGH that evaluated doses as high as 40 grams, participants in the current study received doses of up to 30 grams daily.
The phase II PRECREST trial enrolled 64 adult participants - 19 who knew they carried the mutated form of the HD gene and 45 with a 50 percent risk of having inherited the HD mutation. Genetic testing, results of which were made available only to the study statistician and not to study staff or participants, confirmed the genetic status of those who had previously been tested and revealed an additional 26 presymptomatic carriers of the mutated gene, for a total of 47 participants with presymptomatic HD and 17 controls.
For the first 6 months of the trial, participants were randomized into two groups, regardless of gene status. One group received twice-daily oral doses of creatine, up to a maximum of 30 grams per day, the other received placebo. After that first phase, all participants received creatine for an additional 12 months. Participants were assessed at regular study visits for adverse effects, and dosage levels were adjusted, if necessary, to reduce unpleasant side effects. Additional tests – cognitive assessments, measurement of blood markers and MRI brain scans – were conducted at the trial’s outset, at 6 months and at the end of the study period.
During the first phase of the trial more than three-quarters of those randomized to creatine tolerated a daily dose of 15 grams or more, and more than two -thirds tolerated the full 30-gram dose. Throughout the entire trial, a total of 15 participants – including several who knew they carried the HD mutation – discontinued taking creatine because of gastrointestinal discomfort, the taste of the drug, inconvenience, or the stress of being constantly reminded of their HD risk. Other than occasional diarrhea and nausea, few adverse events were associated with creatine.
In participants who carried the HD mutation, the MRI scans taken at the outset of the trial had revealed significant atrophy in regions of the cerebral cortex and basal ganglia known to be affected by the disease. Followup MRI scans at six months showed a slower rate of atrophy in participants taking creatine compared to those on placebo. At the end of the second phase, the rate of brain atrophy had also slowed in presymptomatic participants that started taking creatine after 6 months on placebo.
In addition to suggesting that creatine could slow the progression of HD, these results also imply that neuroimaging may provide a useful biomarker of disease modification in studies of other potential treatments. While participants with the mutation had performed less well than controls on the cognitive tests at the study outset, creatine treatment had no significant effect on those measures, possibly because the tests were not sensitive enough to detect subtle changes that might occur during such a brief time period, the authors note.
"The results of this trial suggest that the prevention or delay of HD symptoms is feasible, that at-risk individuals can participate in clinical trials – even if they do not want to learn their genetic status – and that useful biomarkers can be developed to help assess therapeutic benefits," says senior author Steven Hersch, MD, PhD, of MGH-MIND. "In addition, we believe our study design sets an important precedent for other genetic diseases and will help inform discussions of how clinical research can coexist with deep concerns about genetic privacy and patient autonomy."
Aging brains need ‘chaperone’ proteins
The word “chaperone” refers to an adult who keeps teenagers from acting up at a dance or overnight trip. It also describes a type of protein that can guard the brain against its own troublemakers: misfolded proteins that are involved in several neurodegenerative diseases.
Researchers at Emory University School of Medicine have demonstrated that as animals age, their brains are more vulnerable to misfolded proteins, partly because of a decline in chaperone activity.
The researchers were studying a model of spinocerebellar ataxia, but the findings have implications for understanding other diseases, such as Alzheimer’s, Parkinson’s and Huntington’s. They also identified targets for potential therapies: bolstering levels of either a particular chaperone or a growth factor in brain cells can protect against the toxic effects of misfolded proteins.
The results were published this week in the journal Neuron.
Scientists led by Shihua Li, MD, and Xiao-Jiang Li, MD, PhD devised a system in which production of a misfolding-prone protein that causes a form of spinocerebellar ataxia can be triggered artificially in mice at various ages. Both Li’s are professors of human genetics at Emory University School of Medicine. The first author of the paper is BCDB graduate student Su Yang.
Spinocerebellar ataxia is an inherited neurodegenerative disease in which patients develop gait problems and a loss of coordination in mid-life, because of atrophy of the cerebellum. There are several types, each caused by a mutation in a different gene.
Most of the mutations that cause spinocerebellar ataxia involve an expansion of a “polyglutamine repeat" in a protein. Having the same protein building block (the amino acid glutamine) repeated dozens of times alters the protein’s function and makes it more likely to misfold and clump together. The misfolded proteins are toxic and interfere with the normal forms of the same protein.
Huntington’s disease is caused by a similar polyglutamine repeat. Misfolded proteins also play roles in Alzheimer’s and Parkinson’s, although their production is not driven by an inherited polyglutamine repeat in those diseases.
Li’s team was trying to distinguish between two possibilities. One was that the duration of mutant protein accumulation is important for disease severity; aging might allow more misfolded proteins to accumulate and become toxic over time.
Instead, the scientists observed that older animals develop disease more quickly after mutant protein production is triggered. The mutant protein accumulates more quickly in 9- and 14-month old mice than in 3-month old mice, suggesting that aged neurons are more vulnerable to the effects of the misfolded protein.
Chaperones are proteins whose job is to “prevent improper liaisons" between other proteins; they prevent the sticky regions of proteins from grabbing something they’re not supposed to. Li’s team identified a particular chaperone called Hsc70 whose activity declines with age in the brain, while others’ activity does not.
To confirm Hsc70’s importance, the researchers showed that boosting cells’ levels of Hsc70 can bolster their ability to cope with misfolded proteins. Injecting mice in the cerebellum with a virus that forces cells to make more Hsc70 can slow degeneration. The researchers found that the mutant protein interferes with production of a growth factor called MANF (mesenchephalic astrocyte-derived neurotrophic factor) in the cerebellum and that Hsc70 can prevent this interference. Injection of a virus that forces cells to make more MANF can also slow degeneration.
Potentially, small molecules that increase Hsc70 or MANF levels could be used for treating spinocerebellar ataxia, says Xiao-Jiang Li.
(Source: news.emory.edu)
Parkinson gene: Nerve growth factor halts mitochondrial degeneration
Neurodegenerative diseases like Parkinson’s disease involve the death of thousands of neurons in the brain. Nerve growth factors produced by the body, such as GDNF, promote the survival of the neurons; however, clinical tests with GDNF have not yielded in any clear improvements. Scientists from the Max Planck Institute of Neurobiology in Martinsried and their colleagues have now succeeded in demonstrating that GDNF and its receptor Ret also promote the survival of mitochondria, the power plants of the cell. By activating the Ret receptor, the scientists were able to prevent in flies and human cell cultures the degeneration of mitochondria, which is caused by a gene defect related to Parkinson’s disease. This important new link could lead to the development of more refined GDNF therapies in the future.
In his “Essay on the Shaking Palsy” of 1817, James Parkinson provided the first description of a disease that today affects almost 280,000 people in Germany. The most conspicuous symptom of Parkinson’s disease is a slow tremor, which is usually accompanied by an increasing lack of mobility and movement in the entire body. These symptoms are visible manifestations of a dramatic change that takes place in the brain: the death of large numbers of neurons in the Substantia nigra of the midbrain.
Despite almost 200 years of research into Parkinson’s, its causes have not yet been fully explained. It appears to be certain that, in addition to environmental factors, genetic mutations also play a role in the emergence of the disease. A series of genes is now associated with Parkinson’s disease. One of these is PINK1, whose mutation causes mitochondrial dysfunction. Mitochondria are a cell’s power plants and without them, a cell cannot function properly or regenerate. Scientists from the Max Planck Institute of Neurobiology and their colleagues from Munich and Martinsried have now discovered a hitherto unknown link that counteracts mitochondrial dysfunction in the case of a PINK1 mutation.
The PINK1 gene emerged at a very early stage in evolutionary history and exists in a similar form for example in humans, mice and flies. In the fruit fly Drosophila, a mitochondrial defect triggered by a PINK1 mutation manifests in the fraying of the muscles. Less visible, the flies’ neurons also die. The scientists studied the molecular processes involved in these changes and discovered that the activation of the Ret receptor counteracts the muscle degeneration. “This is a really interesting finding which links the mitochondrial degeneration in Parkinson’s disease with nerve growth factors,” reports Rüdiger Klein, the head of the research study. Ret is not an unknown factor for the Martinsried-based neurobiologists: “We already succeeded in demonstrating a few years ago in mice that neurons without the Ret receptor die prematurely and in greater numbers with increasing age,” says Klein.
The Ret receptor is the cells’ docking site for the growth factor GDNF, which is produced by the body. Various studies carried out in previous years showed that the binding of GDNF to its Ret receptor can prevent the early death of neurons in the Substantia nigra. However, clinical studies on the influence of GDNF on the progression of Parkinson’s in patients did not lead to any clear improvement in their condition.
The new findings from basic research suggest that the mitochondrial metabolism is boosted or re-established through Ret/GNDF. “Based on this finding, existing therapies could be refined or tailored to specific patient groups,” hopes Pontus Klein, who conducted the study within the framework of his doctoral thesis. This hope does not appear to be completely unfounded: The scientists have already discovered a Ret/GDNF effect in human cells with a PINK1 defect similar to that observed in the fruit fly. It may therefore be possible to search for metabolic defects in the mitochondria of Parkinson’s patients in future. A specially tailored GDNF therapy could then provide a new therapeutic approach for patients who test positively.
Head first: reshaping how traumatic brain injury is treated
Traumatic brain injury affects 10 million people a year worldwide and is the leading cause of death and disability in children and young adults. A new study will identify how to match treatments to patients, to achieve the best possible outcome for recovery.
The human brain – despite being encased snugly within its protective skull – is terrifyingly vulnerable to traumatic injury. A severe blow to the head can set in train a series of events that continue to play out for months, years and even decades ahead. First, there is bleeding, clotting and bruising at the site of impact. If the blow is forceful enough, the brain is thrust against the far side of the skull, where bony ridges cause blood vessels to lacerate. Sliding of grey matter over white matter can irreparably shear nerve fibres, causing damage that has physical, cognitive and behavioural consequences. As response mechanisms activate, the brain then swells, increasing intracranial pressure, and closing down parts of the microcirculatory network, reducing the passage of oxygen from blood vessels into the tissues, and causing further tissue injury.
It is the global nature of the damage – involving many parts of the brain – that defines these types of traumatic brain injuries (TBIs), which might result from transport accidents, assaults, falls or sporting injuries. Unfortunately, both the pattern of damage and the eventual outcome are extremely variable from patient to patient.
“This variability has meant that TBI is often considered as the most complex disease in our most complex organ,” said Professor David Menon, Co-Chair of the Acute Brain Injury Programme at the University of Cambridge. “Despite advances in care, the sad truth is that we are no closer to knowing how to navigate past this variability to the point where we can link the particular characteristics of a TBI to the best treatment and outcome.”
Read moreQuality control of mitochondria as a defense against disease
Scientists from the Montreal Neurological Institute and Hospital in Canada have discovered that two genes linked to hereditary Parkinson’s disease are involved in the early-stage quality control of mitochondria. The protective mechanism, which is reported in The EMBO Journal, removes damaged proteins that arise from oxidative stress from mitochondria.
“PINK1 and parkin, are implicated in selectively targeting dysfunctional components of mitochondria to the lysosome under conditions of excessive oxidative damage within the organelle,” said Edward Fon, Professor at the McGill Parkinson Program at the Montreal Neurological Institute and Hospital. “Our study reveals a quality control mechanism where vesicles bud off from mitochondria and proceed to the lysosome for degradation. This method is distinct from the degradation pathway for damaged whole mitochondria which has been known for some time. It is also an early response, proceeding on a timescale of hours instead of days.”
The deterioration of mechanisms designed to maintain the integrity and function of mitochondria throughout the lifetime of a cell has been suggested to underlie the progression of several neurodegenerative diseases, including Parkinson’s disease. When mitochondria, the “power plants” of the cell that provide energy, malfunction they can contribute to Parkinson’s disease. If they are to survive and function mitochondria need to degrade oxidized and damaged proteins.
In the study, immunofluorescence and confocal microscopy were used to observe how the vesicles “pinch off” from mitochondria with their damaged cargo. “Our conclusion is that the loss of this PINK1 and parkin-dependent trafficking system impairs the ability of mitochondria to selectively degrade oxidized and damaged proteins and leads, over time, to the mitochondrial dysfunction noted in hereditary Parkinson’s disease,” said Heidi McBride, Professor in the Neuromuscular Group in the Department of Neurology and Neurosurgery at the Montreal Neurological Institute and Hospital.
Both salvage pathways are operational in the cell. If the vesicular pathway, the first line of defense, is overwhelmed and the damage is irreversible then the entire organelle is targeted for degradation.
(Source: embo.org)