Unfolded Protein Retention And Endoplasmic Reticulum Stress
Alpha-synuclein was found as a main component of the Lewy bodies and the gene was found to be a causative gene of a rare autosomal dominant PD . It has been reported that multiplication of the gene was to be the cause of the disease . It has been suggested that aggregates of alpha-synuclein cause potentiation of oxidative stress, possibly with interaction with iron.
Synuclein was considered to be degraded in the proteasome. Knockout of the 26S proteasome in the dopaminergic neurons induced pale bodies, which is reported to be a prodrome of the Lewy bodies .
Parkin and UCHL-1 are considered essential for ubiquitination of the unfolded proteins, and the gene mutations were found in some familial PD. It is considered that oxidative stress may lead a combination of Parkin and DJ-1, and the combination suffocates unfolded protein degrad- ation . Mg has also been reported to inhibit spontaneous and iron-induced aggregation of alpha-synuclein .
Scheme of possible pathomechanisms of dopaminergic neuron death in Parkinsons disease.
Serum Metal And Peripheral Blood Mononuclear Cell Gene Expression
The levels of Mg and Zn were assessed in the blood serum of PD and control using AAS. The normality test was conducted, which showed normal distribution of data. Further, Students test was executed that demonstrated that Mg was significantly increased, whereas Zn was significantly decreased in PD compared to control. Similarly, the gene expression of RPL6 was decreased significantly in PD . Furthermore, the interdependency between metal concentrations and gene expression shows RPL6 was negatively correlated with Mg and positively correlated with Zn based on R > 0.90.
Figure 6. Relative expression: Gene expression analysis of 60S ribosomal protein L6 in peripheral blood mononuclear cells of control and PD . The columns represent the average gene expression with standard deviation error bar, and asterisk denotes statistical significance with p-value 0.05.
Table 3. Pearsons correlation between serum metal concentrations with the RPL6 gene expression showing interdependency in Parkinsons disease.
Can Dietary Magnesium Control The Symptoms Of Parkinsons Disease
While the dietary intake of Mg has been shown to reduce the risk of developing Parkinsons disease, whether it relieves the symptoms of the disease is still uncertain. There are some anecdotal evidence suggests that high consumption of Mg could help with relieving some symptoms of the disease. For some people that have tried it are convinced that it works. They got improvement in their tremor and movement . On the contrary, there are people who reported that their symptoms become worse due to high intake of Mg. Therefore, one must be cautious and should take the advice of his doctor before using it.
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Magnesium And Risk Of Parkinsons Disease
Lately, there has been a growing interest in the protective role of Mg in Parkinsons disease. While the specific role of Mg in the development of Parkinsons disease has not been explored yet, a study conducted in Japan showed that low consumption of Mg increases the risk of Parkinsons disease. In this study, 249 Parkinsons patients and 368 controls without brain diseases were examined for their metal consumption. The study concluded that higher intake of Mg decreased the risk of developing Parkinsons disease .
Earlier before this study, it was reported that Mg concentration in the brain of Parkinsons patients decreases with progression of the disease. In this report, brains from 9 Parkinsons disease patients and 12 control subjects were analyzed for different metals. Mg level was found substantially lower in Parkinsons disease brains compared to control brains .; Similar kinds of results were also observed in other studies .
Overall, these studies suggest that Mg has the therapeutic potential to protect the brain from developing Parkinsons disease.
Determination Of Free Intracellular Mg2+ By Mag
The -tet and +tet wt and p.A350V cells were rinsed twice with ice-cold, completely divalent-free, Dulbecco’s phosphate-buffered saline , detached by HyQtase, centrifuged, washed twice in completely Ca2+- and Mg2+-free Hank’s balanced solution supplemented with 10 mM HEPES and 1.36 mM L-glutamine , and finally resuspended in the same solution. Then, the cells were loaded with 7.5 µM mag-fura 2-AM in the presence of the loading-facilitator Pluronic F-127 . After being washed in CMF-HBS+, cells were incubated for a further 30 min at 37°C to allow for the complete de-esterification of the fluorescence probe, washed twice in CMF-HBS+ to remove extracellular mag-fura 2 and stored in CMF-HBS supplemented with 10 mM HEPES, 5 mM glucose, and 0.4 mM Mg2+ until the start of the experiments. Directly before measurements, all cells were Mg2+-loaded by a 20-min pre-incubation in CMF-HBS+ supplemented with 10 mM Mg2+ . Then, after the remaining extracellular Mg2+ had been washed out by rinses in CMF-HBS+, the i of cells was continuously determined for 10 min in CMF-HBS+ ; CMF-HBS+ supplemented with 5 mM Mg2+; or CMF-HBS+ supplemented with 10 mM Mg2+. Differentiation of NME from other transport components was performed by means of the NME inhibitor imipramine or the NME stimulator dB-cAMP , .
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Analysis Of Individual Dataset
Each dataset was background corrected and normalized using Robust Multi-chip Averaging method. Principal component analysis plot was visualized to determine the sample distribution based on gene expression before and after normalization to identify outliers. The differentially expressed genes in PD compared to control was computed using the limma method with p-value < 0.05, adjusted by BenjaminiHochbergs false discovery rate .
Adding Magnesium To Your Diet
Getting magnesium into your diet is fairly easy, with it being found in several different foods and available in supplements.
The amount you need each day is dependent on age and sex:
- Men: 400 to 420 mg
- Women: 310 to 320 mg
- Pregnant women: 350 to 360 mg
Youre likely to hit your recommended daily intake by eating foods such as:
- Legumes, nuts, seeds, whole grains, and green leafy vegetables
- Fortified breakfast cereals and other fortified foods
- Milk, yogurt, and some other milk products
Unfortunately, many diets in the U.S. arent meeting their magnesium recommended intake, with the National Health and Nutrition Examination Survey stating that number is as high as 79% of U.S. adults.
Always check with your doctor first, but a magnesium supplement may be beneficial to ensure youre hitting your daily intake. Magnesium is also often found in multivitamins and other dietary supplements. According to the National Institute of Health , the easily digested forms of magnesium in supplements include:
- Magnesium aspartate
- Magnesium lactate
- Magnesium chloride
If youre looking for a multivitamin supplement, look no further than Natural Wellnesss iron-free multivitamin which contains chelated magnesium another easily absorbed form.
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Diet And Exercise For Parkinsons
If your symptoms are mild, focus on vigorous exercise such as running, cycling and circuit training
If your symptoms are progressing, focus on exercise that takes effort and pushes you
If your symptoms are more complex, concentrate on everyday movements and activities you find difficult getting up from a chair, for example
As An Inhibiter Of Oxidative Stress
The present authors conducted a study to clarify the effects of Mg administration in a rat PD model involving culture of ventral mesencephalic- striatal cells with 1-methyl-4-phenylpyridinium , based on recent evidence for significant loss of dopaminergic neurons exclusively in the substantia nigra of 1-year-old rats after exposure to low Mg intake over generations . The results indicated that Mg might protect dopaminergic neurons in the substantia nigra from degeneration. The concentration of Mg in the culture medium varied from 0.8 mM, corresponding to the control condition, to 4.0 mM. Effects were estimated by counting the number of surviving dopaminergic neurons immunopositive for tyrosine hydroxylase and measuring the length of dopaminergic neurites. An increase in the concentration of Mg to 1.2 mM significantly inhibited the toxicity of MPP+, and a concentration of 4.0 mM completely prevented any decrease in the number of dopaminergic neurons. The length of dopam- inergic neurites was significantly preserved in the presence of Mg at 1.2 and 4.0 mM. An increase in the concentration of Mg to 1.2 and 4.0 mM led to a significant amelioration in the length of dopam- inergic neurites after MPP+ toxicity .
Prevention of MPP+ toxicity by Mg in a Parkinson model . a: normal condition of cultured nigral dopaminergic neurons. b: severe loss of dopaminergic neurons and the neuritis after MPP+ administration. c: An increase in the concentration
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How About Mg Supplementation In Parkinsons
Mg supplementation has been found protective against Parkinsons in animal studies. In these studies, Mg was shown to protect brain cells that are lost in Parkinsons. These cells are called dopaminergic neurons and their loss is the main reason for developing this disease.;
In a laboratory study, when brain cells from 1-year old rats were exposed to a neurotoxin, a chemical that caused changes in the brain similar to Parkinsons, a significant loss of dopaminergic neurons was observed. But when the same brain cells were treated with a high concentration of Mg before exposure to the same neurotoxin, the loss of dopaminergic neurons was rescued.;
In another study, Mg intake was found to stop the abnormal behaviors of protein in the brain that caused the death of dopaminergic neurons and develop Parkinsons.;
While results from these animal studies are exciting, there has not been a study conducted on humans that could show that its supplementation treats the symptoms or stop the disease progression.;
There is some anecdotal evidence suggesting that using Mg supplements could help with relieving some symptoms of the disease. For some people that have tried it are convinced that it works. They got improvement in tremor and movement. On the contrary, there are people who reported that their symptoms become worse due to the high intake of Mg. Therefore, one must be cautious and should take the advice of a doctor before using it.
Parkinsons And Nutrition: Food For Thought
Scientific and Medical Senior Director
A healthy lifestyle and balanced nutrition are essential pillars of good health for all people.A balanced diet is even more critical for people with a neurodegenerative condition, such as Parkinson’s disease .
PD influences many systems in the body, making those living with PD susceptible to malnutrition. Involuntary movements associated with PD result in increased energy expenditure. Constipation caused by slowed gastrointestinal transit, disease symptoms , and medication side effects can all limit food consumption. In addition, one of the most used medications, levodopa, competes with proteins for absorption from the small intestine.Although no single specific diet is recommended for everyone with PD, there has been growing research on the potential health benefits for PD patients of a balanced diet that includes high quality and nutritional food. Nutrition may affect PD patients wellbeing in several ways, from neuroprotection to symptom relief. This article provides a taste of the latest research in the field.
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Antibiotics Interacts With Magnesium
Some antibiotics can affect the muscles. These antibiotics are called aminoglycosides. Magnesium can also affect the muscles. Taking these antibiotics and getting a magnesium shot might cause muscle problems.Some aminoglycoside antibiotics include amikacin , gentamicin , kanamycin , streptomycin, tobramycin , and others.
What Is Parkinsons Disease
Parkinsons Disease is a progressive neurological disorder which affects around 120,000 people in the UK. Progressive means that it typically worsens over time and neurological means that it affects the nervous system . The main symptoms of Parkinsons are slowness of movement , rigidity, tremor and postural instability . While Parkinsons is typically described as a movement disorder, a person with Parkinsons may experience a range of other symptoms including constipation, low mood, fatigue, sleep and memory problems. Symptoms of Parkinsons can be grouped into two major categories motor symptoms and non-motor symptoms .
Parkinsons typically strikes in middle age, with around 80% of cases presenting between ages of 40 and 70, and progression of symptoms is generally slow and continuous. Younger people who develop Parkinsons are more likely to have a relative with the illness suggesting a stronger genetic component. Symptoms usually begin gradually and motor symptoms are often preceded by non-motor symptoms such as fatigue, loss of smell, depression, constipation and sweating abnormalities.
If you are concerned that you or a friend or family member has symptoms of Parkinsons, you or they should see a GP immediately.
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Naturalremedy For Parkinsons #7 Omega
Animal based omega-3 fatty acids are a powerful weapon inthe fight against Parkinsons disease. One of the main fatty acids, DHA, is oneof the essential building blocks for the human brain. Half of your brain andeyes are made up of fat and a large proportion of this is DHA fat.
Omega-3 fatty acids have the unique ability to cross theblood-brain barrier, something most conventional drugs cannot do. They helpincrease dopamine levels and reduce neuroinflammation in the brain, while atthe same time, stimulating neuron growth. So basically, EPA and DHA help preventbrain cell damage and keep the nervous system in tip top working order! ;4;
Best sources of animal based omega-3s are either fishoil, cod liver oil or krill oil. High strength krill oil is the preferred option as thiscontains a substance called Astaxanthin. Astaxanthin is a potent brain food nutrientthat has been shown to prevent neurodegeneration and inflammation of the brain.For dosages, take AT LEAST the highest recommended amount listed on the bottle the same goes with fish oil or cod liver oil. You cant overdose on thesesupplements so theres nothing to be concerned about. In fact, the more omega-3syou can get into you the better the results!
In addition to this, try and eat some cold water fattyfish such as salmon, tuna, mackerel, sardines or herring 3-4 times a week foran extra supply of DHA and EPA.;
Quantitative Real Time Pcr
To determine the transcription activity of both transgenic variants of SLC41A1, namely wt and c.1049C>T, by the quantitative real time PCR method in induced and non-induced cells, we used the following primers: hSLC41A1fw, 5-TTGGACGCTCGCCTTGCCTG-3 and hSLC41A1rev, 5-TGGTGTGGAACACCTGCGCC-3. Expression activities of SLC41A2 and SLC41A3 were determined with following primer pairs: hSLC41A2fw, 5-TGGTTATAAGTAGCATTGGGGGCCT-3 and hSLC41A2rev, 5-TCCTGCTAGCCTGAATGGCCA -3; hSLC41A3fw, 5-CACAAAGATAGTCGGTATCTGACG-3and hSLC41A3rev, 5-GACCATGGCCAGGATGATT-3. Total RNA isolation, the determination of its integrity, purity, and quantity, cDNA synthesis, and q-RT-PCR were performed as described by Kolisek and colleagues . Data were evaluated with software application FK-Wolf-01, developed by Katharina Wolf . Statistical evaluation was performed with data sets acquired from three biological preparations for each condition loaded in triplicate.
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Natural Remedy For Parkinsons #4 Chlorella And Borax:
If you have a neurological disease such as Parkinsons orAlzheimers, the importance of removing heavy metals from the body – especiallyfrom the brain and nervous system – cannot be overstated. Heavy metalsaccumulate in the brain and nervous system at a rapid rate and cause damage tothe neurological pathways and brain inflammation. Fluoride is one ofthe worst, however, mercury, lead, aluminium and cadmium are also extremely dangerous.Chlorella and borax not only remove these heavy metals completely, theycontinue to prevent further toxic build-ups.
Chlorella is a miracle blue-green algae and one of themost powerful detoxifiers and chelators yet discovered. Whenits combined with cilantro, its benefits are enhancedsignificantly. A Russian study found that chlorella, combined with cilantro,was able to remove all heavy metals from the body, including fluoride and mercury,with no adverse or harmful side effects. You can purchase chlorellain powdered form online or from most health food stores. Just make sure you buythe Broken Cell Wall Chlorella as this is the strongest and most bio-available.For dosage recommendations, simply follow the directions on the container.
What The Research Is Saying
According to a recent 2021 study published in the Journal of Hepatology it was found that both patients and mice that had non-alcoholic steatohepatitis also had high amounts of cyclin M4 protein. This protein has a job of transporting magnesium out of the liver. It is the responsible party behind the imbalance of magnesium levels that can lead to liver disease development.
These patients have an altered magnesium export machinery that increases the vulnerability of their liver to suffer inflammatory processes, development of fibrosis and fat deposition, Malu Martinez Chantar, first author in the publication, told NYU in an interview . This study also presents a novel therapeutic approach based on GalNAc-siRNA technology that specifically targets the liver by modulating CNNM4 levels. The CNNM4 molecule developed from Silence Therapeutics proprietary mRNAi GOLD Platform effectively protects from liver pathology in preclinical models of steatohepatitis.
To make things a little less complicated, basically siRNA is a drug that has shown potential to treat various diseases including cancer and Parkinsons disease. N-acetylgalactosamine siRNA was developed specifically for liver delivery.
With this treatment targeting CNNM4 and decreasing its quantity steatosis, inflammation, and fibrosis are all alleviated in NASH models. Not only that, but it helps magnesium accumulate back into the liver and reduces stress on the endoplasmic reticulum .
Optimise Your Diet Reduce Your Toxic Load
While the cause of Parkinsons is not known, environmental toxins such as pesticides and herbicides are implicated. Researchers have found levels of these chemicals to be higher in the brains of Parkinsons sufferers and incidence of Parkinsons is higher in areas with greater use of these chemicals. It makes sense to avoid any environmental toxins that you can. Also, consider your intake of dietary toxins such as alcohol and caffeine avoiding or reducing these may reduce the load on your bodys detoxification pathways.
Naturaltreatment For Parkinsons #9 Exercise And Other Alternative Therapies:
Regular exercise has been shown to help Parkinsonssufferers by reducing muscle stiffness, increasing mobility, and enhancing postureand balance. Exercise also increases oxygen levels and neurotransmitters, alongwith releasing potent mood elevating chemicals called endorphins.
The type of exercise performed for PD is crucial. Aqua orwater aerobics can be particularly useful as traditional exercise is usuallyquite difficult for many Parkinsons sufferers. Muscle decline, loss of strength,stiffness and loss of balance can make conventional exercises difficult toperform. The great thing about aqua aerobics is it still has the same benefits as other exercise regimens,but the risk of falling is eliminated.
Other types of exercises that can be beneficial for PDsufferers include Tai Chi, Yoga, dancing, walking, aerobic/jazzercise classes,and general stretching.
For more information on the different exercise programsavailable for Parkinsons patients, you can check out this website ;Exercise and Physical Therapy for ParkinsonsDisease
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