Mitochondrial Dysfunction: A Pivotal Pathological Mechanism Of Parkinsons Disease
Mitochondria are complex cytosolic organelles of eukaryotic cells whose primary function is the generation of cellular energy in the form of ATP by oxidative phosphorylation. Mammalian mitochondria contain between 2 and 10 mitochondrial DNA molecules encoding 22 transfer RNAs, two ribosomal RNAs, and 13 polypeptides, each of which is part of the respiratory chain and the oxidative phosphorylation system . The mitochondrial respiratory chain contains four protein complexes that form the site of oxidative phosphorylation. This site is responsible for NADH and FADH2 oxidation, co-occurring with the movement of protons from the matrix into the intermembrane space. This movement produces an electrochemical gradient denoted as mitochondrial membrane potential . This gradient stimulates the ATP synthase to reduce molecular oxygen and synthesize ATP. This step is fundamental in aerobic metabolism and constitutes the primary provider of ATP at the final stage of cellular respiration . Nevertheless, the biological function of mitochondria goes far beyond energy production and includes the metabolism of lipids and amino acids and the support of intermediate metabolic pathways, such as the Krebs cycle.
Patients Should Seek A Medication Review At Least Annually
There have been several exciting recent developments in the realization of advanced treatment options and new medications for Parkinsons disease. From surgical treatments to drug development to a pump that infuses medication to patients throughout the day, individuals with Parkinsons disease may benefit from the latest developments for treatment of PD.
Most patients with Parkinsons disease can be adequately treated the first several years after the disease has begun presenting symptoms with medications that deliver levodopa, used alone or in combination with carbidopa. Later in the disease, individuals with PD may consider highly effective surgical treatments such as Deep Brain Stimulation and/or other medications or combinations of medications to manage their symptoms.
Trey Eskew, a physicians assistant who has treated patients at Neurology Solutions Movement Disorders for the past six years, said that many patients arent aware of the new PD medications that have become available, including several that were released in 2015.
Here are some facts and findings about the latest PD medications.
Treatment Of Neurobehavioral Features
Treatment of cognitive deficits associated with PD is as challenging as the treatment of Alzheimers disease and other dementias. While the general assumption has been that cognitive deficits are a feature of late-stage PD, clinically inapparent cognitive changes on neuropsychiatric testing may be found . With the introduction of cholinesterase inhibitors such as donepezil , rivastigmine , and galantamine and the NDMA antagonist memantine , it is possible that cognition, orientation and language function will improve, and that such improvement will lead to a meaningful improvement in function. Both donepezil and rivastigmine improve cognition to the same effect, but donepezil is better tolerated . The largest and best-designed study of rivastigmine in dementia associated with PD involved 541 patients enrolled in a 24-week randomized, multicenter, double-blind clinical trial . The patients had a relatively mild dementia , with onset of dementia about 2 years after onset of PD symptoms. The mean ADAS-cog score, the primary efficacy variable, improved by 2.1 points in the rivastigmine group, compared to 0.7 in the placebo group , and the MMSE improved by 0.8 in the rivastigmine group and worsened by 0.2 in the placebo group . At the end of the study, 55.5% were receiving 9 to 12 mg. The adverse effects that were significantly more frequent in the rivastigmine group were nausea, vomiting, dizziness, and tremor.
Parkinsons Disease Medications: The Facts
There have been many developments in Parkinson’s disease treatments in recent years. As such, doctors now have a greater understanding of traditional Parkinson’s disease medications and their side-effects. Scientists have also developed new drugs to help control tremors, slowed movement and other Parkinson’s symptoms.
Before we explore the best medication for Parkinson’s disease, it’s important to address the facts. Firstly, Parkinson’s disease medications cannot cure your condition, nor will they slow down the progression of your symptoms. These medications are prescribed to help patients live independently and improve their quality of life.
It’s important to note that some patients do not respond well to Parkinson’s disease medications. In this case, there are plenty of other treatment options to consider such as homeopathic remedies, physical therapy and surgical intervention. Again, none of these treatments provides a cure, but they can help ease or control your symptoms.
What Is Parkinsons Disease Surgery
Parkinson’s disease surgery is a brain operation called deep brain stimulation . The surgery is also used to treat epilepsy, obsessive-compulsive disorder and a condition called “essential tremor.” DBS is widely considered one of the most significant neurological breakthroughs in recent history, posing a potential treatment for major depressive disorder, stroke recovery and addiction. Parkinson’s disease brain surgery aims to interrupt problematic electrical signals from targeted areas in the brain and reduce PD symptoms.
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Progress In The Treatment Of Parkinsons Disease
Despite the fact that 200 years passed since the discovery of PD, it was not until later in the 20th century that progress in the treatment of PD was achieved, predominantly due to the limited understanding of PD pathophysiology. Given Carlssons discoveries of DAs involvement in the 1950s, it became clear that PD development involved dopaminergic cell death and a decrease of DA in the striatum and other structures of the forebrain. The first steps towards treatment were made by Carlsson , who proposed targeting this DA deficiency to facilitate symptom reduction.
Indulge Yourself In The Following Activities As A Part Of Parkinsons Disease Treatment
A Daily Walk
If you cannot afford for a workout, you can at least afford for a daily walk, anytime in a day. However, working out is not much recommended for patients undergoing Parkinsons disease treatment as the muscles and nerves should be treated carefully without any rigid movement.
You can have a stroll around your nearby park to relax and have the best time. A regular morning, as well as an evening walk, can show a tremendous effect on your physical movement. It helps in relieving you from the stiffness and brings more flexibility to your body.
Some Simple Stretches
Simple stretches are recommended for people undergoing Parkinsons disease treatment as this is going to bring flexibility in the body and improve your movement day after day. The stretches mentioned are very elementary and are very effective in the reducing the effects of Parkinsons disease.
You can practice this at any time in your home. Stay about 2 feet away from the wall. Place both hands on the wall and lean forward. Bend your knee forward and stay in the position for twenty seconds. Shift the leg and repeat the same.
Stand erect with both the hands placed on either side of your body. Lift one of your legs and try to grab the foot of your leg with the respective side of your hand. Hold for 30 seconds and remain in the position. Relax and repeat the same with another leg.
Standing Cow Face Pose
Practice the same with the alternate hand.
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What Are The Most Common Medicines Used To Treat Pd
Levodopa is the most commonly prescribed and most effective medicine for controlling the symptoms of PD, particularly bradykinesia and rigidity.
Levodopa is a chemical found naturally in our brains. When given as a medicine, it is transported to the nerve cells in the brain that produce dopamine. It is then converted into dopamine for the nerve cells to use as a neurotransmitter.
Sinemet is made up of levodopa and another drug called carbidopa. Levodopa enters the brain and is converted to dopamine while carbidopa prevents or lessens many of the side effects of levodopa, such as nausea, vomiting, and occasional heart rhythm disturbances. It is generally recommended that patients take Sinemet on an empty stomach, at least ½ hour before or one hour after meals.
There are two forms of Sinemet: controlled-release or immediate-release Sinemet. Controlled-release Sinemet and immediate-release Sinemet are equally effective in treating the symptoms of PD, but some people prefer the controlled release version. Ask your doctor which approach is best for you.
Dopamine agonists are medicines that activate the dopamine receptor. They mimic or copy the function of dopamine in the brain.
Parlodel®, Requip®, and Mirapex® are all dopamine agonists. These medicines might be taken alone or in combination with Sinemet. Generally, dopamine agonists are prescribed first and levodopa is added if the patient’s symptoms cannot be controlled sufficiently.
Natural Treatment For Parkinsons #3 Turmeric And Otherherbs And Spices:
A recent study published in the journal Stem Cell Research & Therapy, foundthat the extracts in turmeric, particularly curcumin and the newly discovered Ar-turmerone,can regenerate a damaged brain and reverse neurological disorders. Researchers said Ar-turmerone is a promising candidate to supportregeneration in neurologic disease. Michigan State University researcherBasir Ahmad also found that a compound in turmeric may help fight Parkinsonsdisease by disrupting the proteins responsible for the disease.
Another study published in the Pharmacognosy Magazine found that tumeric can prevent and evenreverse the toxic effects exerted on the brain from fluoride exposure. Fluorideis a nasty and dangerous heavy metal that destroys brain cells and the intricateworkings of the central nervous system. Fluoride poisoning has also beenimplicated in the development of neurological diseases such as Alzheimers,Parkinsons, ALS and multiple sclerosis. 7
Turmeric is also a very potent anti-inflammatory spice. Because Parkinsons is aninflammation type disease, turmeric will help immensely. A heaped teaspoon ofhigh quality turmeric powder taken 3 times daily in asmoothie will do the trick. Just make sure you combine it with 10-12 blackpeppercorns for enhanced absorption Turmeric is also fat soluble so youll need tocombine it with some coconut oil, red palm oil or fish/krill oil as well.
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How Do I Prevent Falls From Common Hazards
- Floors: Remove all loose wires, cords, and throw rugs. Minimize clutter. Make sure rugs are anchored and smooth. Keep furniture in its usual place.
- Bathroom: Install grab bars and non-skid tape in the tub or shower. Use non-skid bath mats on the floor or install wall-to-wall carpeting.
- Lighting: Make sure halls, stairways, and entrances are well-lit. Install a night light in your bathroom or hallway and staircase. Turn lights on if you get up in the middle of the night. Make sure lamps or light switches are within reach of the bed if you have to get up during the night.
- Kitchen: Install non-skid rubber mats near the sink and stove. Clean spills immediately.
- Stairs: Make sure treads, rails, and rugs are secure. Install a rail on both sides of the stairs. If stairs are a threat, it might be helpful to arrange most of your activities on the lower level to reduce the number of times you must climb the stairs.
- Entrances and doorways: Install metal handles on the walls adjacent to the doorknobs of all doors to make it more secure as you travel through the doorway.
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.
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Other Dopamine Replacement Drugs
Although levodopa is the gold standard and generally accepted to be the most effective treatment for Parkinsons, there are a few other options. Since we know that long-term levodopa use can lead to the movement issues of dyskinesia, you might want to try another medication first37 . Some dopamine replacement drugs can also help levodopa work better.
A dopamine agonist drug directly stimulates your dopamine receptors in your brain, similar to how real dopamine would. In order to carry out its functions in the body, dopamine must first attach to receptor proteins in the brain, which help signal other cells on how to behave. While dopamine agonists dont turn into dopamine the way levodopa does, they stimulate dopamine receptors without binding to them and ultimately have similar effects in the brain. You can use an agonist instead of levodopa , or in combination with levodopa. You might also use an agonist if avoiding dyskinesia is a priority for you.
Brand name dopamine agonists include Mirapex , Requip , Neupro , and Apokyn .
Its important to note that agonists can cause serious side effects.6 One side effect is impulse control disorders, such as problems with gambling, obsession with sex or shopping. Other possible side effects include hallucinations and excessive daytime sleepiness. Quitting an agonist suddenly can also bring on withdrawal symptoms.
Consider A Medication Review
If you are interested in undergoing a medication review or would like to learn more about new medications for Parkinsons, please contact Neurology Solutions or call for information and to make an appointment. Read on for information on How to Prepare for Your Neurologist Appointment.
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Dopaminergic Input And Organizational Features Of The Dorsal And Lateral Striatum
As reviewed above, it is generally accepted that dysfunction in PD stems from the degeneration of SNc neurons , which leads to motor dysfunction and the loss of VTA neurons , which leads to behavioral dysregulation, including demotivation, anhedonia, and depression within PD . While both pathways have been studied extensively across an array of conditions and pathologies, the modulatory mechanisms of the nigrostriatal pathway neurons have been fairly well described while the varied mechanisms and roles of VTA efferents continue to be elucidated. Within the nigrostriatal pathway, GABAergic medium spiny neurons of the dorsal/lateral striatum receive excitatory glutamatergic signals that can be modulated via dopaminergic inputs originating from the SNc. MSNs are moderately sized cells with large, multi-structured dendritic arbors that constitute a staggering 95% of all postsynaptic nigrostriatal neurons . Local circuit interneurons of the dorsal striatum are also actively involved in regulating MSN activity and can be subdivided into cholinergic interneurons and aspiny GABAergic interneurons known as low-threshold, fast-spiking neurons . Striatal cholinergic and MSNs express several neurotransmitter receptors including the -aminobutyric acid , glutamate, DA, adenosine, serotonin, opioids, and substance P receptors .
How Parkinson’s Disease Is Treated
Claudia Chaves, MD, is board-certified in cerebrovascular disease and neurology with a subspecialty certification in vascular neurology. She is an associate professor of neurology at Tufts Medical School and medical director of the Lahey Clinic Multiple Sclerosis Center in Lexington, Massachusetts.
The treatment options for Parkinson’s disease include several different medications, surgical procedures, and physical therapies. What’s appropriate for you depends on the symptoms you’re experiencing and how severe your disease is. You will most likely benefit from treatments for your tremors and other motor symptoms, but other options for some of the non-motor effects of Parkinson’s disease may also be beneficial for you.
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Management Of Medication Side Effects
Many of the treatments that are commonly used for treatment of Parkinson’s disease may produce distressing side effects. Hallucinations can be a side effect of Parkinsons medications and some people may need to take antipsychotic medications to reduce them.
Dyskinesias are involuntary movements that often result from long-term use of Parkinsons disease medications. Gocavri is approved for treatment of dyskinesia in Parkinson’s disease, and surgery is another potential treatment for this side effect.
What Lifestyle Changes Can I Make To Ease Parkinsons Symptoms
Exercise: Exercise helps improve muscle strength, balance, coordination, flexibility, and tremor. It is also strongly believed to improve memory, thinking and reduce the risk of falls and decrease anxiety and depression. One study in persons with Parkinsons disease showed that 2.5 hours of exercise per week resulted in improved ability to move and a slower decline in quality of life compared to those who didnt exercise or didnt start until later in the course of their disease. Some exercises to consider include strengthening or resistance training, stretching exercises or aerobics . All types of exercise are helpful.
Eat a healthy, balanced diet: This is not only good for your general health but can ease some of the non-movement related symptoms of Parkinsons, such as constipation. Eating foods high in fiber in particular can relieve constipation. The Mediterranean diet is one example of a healthy diet.
Preventing falls and maintaining balance: Falls are a frequent complication of Parkinson’s. While you can do many things to reduce your risk of falling, the two most important are: 1) to work with your doctor to ensure that your treatments whether medicines or deep brain stimulation are optimal and 2) to consult with a physical therapist who can assess your walking and balance. The physical therapist is the expert when it comes to recommending assistive devices or exercise to improve safety and preventing falls.
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