ISLAMABAD, May 24 (Online): The currently agreed-on premise is that the clumping of certain proteins in the brain is a driving factor for Alzheimer\u2019s disease.Researchers from The Buck Institute for Research in Novato, CA, now say there are other proteins in these brain clumps that have been largely ignored so far, and that could also play a role in the development of this form of dementia.<\/p>\n
Using a worm model, scientists found that both the natural aging process and beta-amyloid drive some proteins to become insoluble.
\nResearchers used a compound to boost the quality of mitochondrial health in the proteins that had become insoluble, helping to delay the toxic effects of beta-amyloid.
\nAlthough scientists still do not know the exact cause of Alzheimer\u2019s disease, most agree that the clumping of certain proteins \u2014 beta-amyloidTrusted Source and tauTrusted Source \u2014 in the brain characterize the disease.<\/p>\n
\u201cThe unifying feature of neurodegenerative diseases of aging is the accumulation of large protein clumps in the brain which we term insoluble protein aggregates,\u201d Edward Anderton, PhD, a postdoctoral researcher at The Buck Institute for Research on Aging in California and co-first author of a study recently published in the journal GeroScience, explained to Medical News Today.<\/p>\n
\u201cIn Alzheimer\u2019s disease, the [beta-amyloid] protein forms aggregates called plaques, and these are tightly associated with areas of neuronal death and brain inflammation causing disease,\u201d he noted.<\/p>\n
However, Anderton added, these plaques contain hundreds of additional proteins which have been largely ignored until now.<\/p>\n
For this reason, he and other researchers from The Buck Institute for Research on Aging in California decided to examine how the accumulation of insoluble proteins, in general, might accelerate Alzheimer\u2019s disease.<\/p>\n
Using a worm model, scientists found that both the natural aging process and beta-amyloid drive other proteins to become insoluble.<\/p>\n
Researchers then used a compound to boost the quality of mitochondrialTrusted Source health in the proteins that had become insoluble, effectively delaying the toxic effects of beta-amyloid.<\/p>\n
Mitochondria, the so-called powerhouses of the cell, have recently become a focus point in Alzheimer\u2019s research, as scientist have been trying to see whether \u201crepairing\u201d mitochondria that stop functioning well with age might help preserve brain health.<\/p>\n
What is protein clumping?
\nAccording to Manish Chamoli, PhD, research scientist at The Buck Institute for Research on Aging in California and co-first author of this study, proteins are like tiny machines in our cells that need to be a specific shape to work correctly.<\/p>\n
\u201cImagine if you had a key that got bent and no longer fit into its lock \u2014 that\u2019s similar to what happens when proteins lose their shape,\u201d Chamoli explained to MNT. \u201cThese misshapen proteins start sticking together and form insoluble protein aggregates. Proteins can lose their shape due to various factors like stress, aging, or damage.\u201d<\/p>\n
\u201cOur cells have evolved ways to either refold the proteins into the correct shape or degrade them when they\u2019re too damaged to be refolded,\u201d he continued.<\/p>\n
In conditions such as Alzheimer\u2019s disease, however, the brain does not correctly dispose of such proteins.<\/p>\n
\u201cIn laboratory organisms, such as the microscopic worm Caenorhabditis elegansTrusted Source, our lab and other labs around the world have observed that, as these worms age, they accumulate clumps of insoluble proteins,\u201c Chamoli told us.<\/p>\n
\u201cLikewise, it\u2019s well established that Alzheimer\u2019s disease patients\u2019 brains accumulate protein aggregates,\u201d he added.<\/p>\n
Why do proteins clump in the brain?
\nAs insoluble proteins do accumulate in the brain during normal disease-free aging, Chamoli, Anderton, and their team wanted to know what was the connection between brain protein clumps in normal aging and Alzheimer\u2019s disease.<\/p>\n
Using a worm model, scientists discovered that beta-amyloid causes a massive amount of insolubility in other proteins, especially in a subset of proteins researchers called \u201cthe core insoluble proteome.\u201c<\/p>\n
According to researchers, the insoluble proteins found in the core insoluble proteome have already been linked to other neurodegenerative conditions including Parkinson\u2019s disease and Huntington\u2019s disease.<\/p>\n
\u201cData suggest there may be a causal role for the insoluble proteome in Alzheimer\u2019s disease pathogenesis,\u201d Anderton said. \u201cFor example, insoluble protein extracts from old but not young animals accelerate the aggregation of [beta-amyloid].\u201d<\/p>\n
\u201cWe questioned if the reverse was also true: Can [beta-amyloid] drive the insolubility of proteins that tend to aggregate during aging? Our data are consistent with the notion that [beta-amyloid] and age-related changes interact in a destructive feedforward cycle, leading to an acceleration of protein insolubility in Alzheimer\u2019s disease.\u201d<\/p>\n
Can boosting mitochondrial health prevent toxic aggregate formation?
\nNext, researchers wanted to find a way to potentially reverse how beta-amyloid helps drive the insolubility of proteins.<\/p>\n
As many mitochondrial proteins become insoluble during natural aging and beta-amyloid influence, they hypothesized that boosting mitochondrial protein quality might reverse some of beta-amyloid\u2019s negative effects.<\/p>\n
\u201cMitochondria contain a specialized energy-producing complex of proteins called the electron transport chainTrusted Source, which is the primary way our cells use food to produce energy,\u201d Chamoli said. \u201cWe found that the proteins of the electron transport chain were driven to become insoluble when we exposed them to [beta-amyloid].\u201d<\/p>\n
\u201cIt has been known for some time that mitochondria can be negatively impacted by [beta-amyloid] but we show that this is likely due to protein insolubility,\u201d he continued. \u201cLuckily, cells possess a way to recycle damaged mitochondria through a process called mitophagyTrusted Source. Our lab and others study a small molecule that boosts mitophagy to rejuvenate mitochondria.\u201d<\/p>\n
To do this, they chose urolithin ATrusted Source \u2014 a metabolite compound found in the gut microbiome. Pomegranates, walnuts, strawberries, raspberries, chia seeds, hemp seeds, and almonds are all foods rich in urolithin A.<\/p>\n
\u201cWe reasoned that using a pharmacological approach to clear away the insoluble proteins from mitochondria could prevent some of the toxic effects of [beta-amyloid] and that\u2019s exactly what we found,\u201d Anderton said.<\/p>\n
Potential for new therapeutic interventions for Alzheimer\u2019s
\nMNT also spoke with Verna R. Porter, MD, a board-certified neurologist and director of the Dementia, Alzheimer\u2019s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute in Santa Monica, CA, about this study.<\/p>\n
Porter, who was not involved in the research, said these findings suggest that beta-amyloid likely contributes to widespread protein insolubility, particularly affecting mitochondrial proteins and that this insolubility mirrors changes seen in aging.<\/p>\n
\u201cThe discovery that targeting mitochondrial health can mitigate some of these aging effects suggests a potential novel approach to addressing Alzheimer\u2019s disease,\u201d she added.<\/p>\n
Porter said that with the study\u2019s findings indicating that improving mitochondrial health may reverse some negative effects of beta-amyloid toxicity, this could pave the way for several potential interventions including pharmacological approaches, nutritional supplements, and lifestyle modifications.<\/p>\n
\u201cIt would be interesting to conduct clinical trials to test the efficacy of mitochondrial health-boosting compounds in Alzheimer\u2019s disease patients, including compounds like urolithin A and other mitochondrial enhancers,\u201d Porter continued.<\/p>\n","protected":false},"excerpt":{"rendered":"
ISLAMABAD, May 24 (Online): The currently agreed-on premise is that the clumping of certain proteins in the brain is a driving factor for Alzheimer\u2019s disease.Researchers from The Buck Institute for Research in Novato, CA, now say there are other proteins in these brain clumps that […]<\/p>\n
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