Providing resources and ideas for therapies and medical developments for Parkinson's disease:
Parkinson's disease is a degenerative disorder affecting the dopaminergic neurons (neurons which produce dopamine) in the mid-region of the brain in the "Substantia Nigra" (where the motor neurons are located) causing a loss of motor skills, tremors, rigidity and slowness of movement (bradykinesia). The dysfunction and death of neurons diminishes the amount of dopamine available for communication with the nervous system to the muscle to perform movement of limbs and motor function. The dysfunction and death of neurons in this region of the brain are caused by an aggregation of a mis-folded protein called alpha-synuclein which either pass through the cell wall (Endocytosis) into the neuron or are natively resident in the neuron but due to its mis-folding and aggregation into insoluble, densely packed "fibrils", are not reprocessed by the cell's own lysosomes or passed out, but are accumulated as a plaque waste product known as Lewy bodies until the neuron cell becomes dysfunctional or bursts (Lysis). Properly folded, soluble alpha-synuclein proteins are an integral part of the neuron cell's repair apparatus and synaptic communication but the formation of Lewy bodies are found to be detrimental and eventually lethal to the neuron cell.The synuclein family of proteins:
Alpha-synuclein (α-synuclein) is a dynamic protein, taking on various folded shapes and aggregating in chains (polymers: one dimensional chain also known as a dimer), depending on its intended purpose.
Neuron cell chaperones, lysosmes and proteasomes (biological elements within a neuron cell) actively recycle alpha-synuclein proteins to keep the alpha-synuclein quantities and chain lengths in balance.
When the alpha-synuclein protein polymer chains become too long to process, they form oligomers (three dimensional structure) and ultimately fibrils which aggregate into Lewy bodies.
The presense of a mis-folded alpha-synuclein will cause other alpha-synuclein proteins to change and mis-fold and can cause a cascading effect which spreads from neuron to neuron in a mechanism called permissive templating or prion like propagation (the mechanism of mad cow disease), resulting in massive neuron dysfunction or death and causing Parkinson's symptoms.
Reference Role of Different Alpha-Synuclein Strains in Synucleinopathies.
The dopamine producing neurons in the Substantia Nigra have long axons which extend to the putamen and caudate nucleus regions of the brain to release dopamine there to control muscle movement. Dopamine is the signalling molecule responsible for providing communications from the brain. As dopamine producing neurons are lost, communications and movement becomes inhibited.
Parkinson's disease becomes noticeable when the about 60% to 70% of the dompamine producing neurons in the Substantia Nigra have been lost, either by cellular death or by becoming dormant and dysfunctional. Korean researchers at IBS, KIST and AMC institutes have found that for those with mild Parkinson's progression, that 55% of the dopamine neurons could be dormant while for those with severe and advanced stages of Parkinson's, about 27% of dopamine neurons could be dormant, leaving open the possibility that these dormant neurons could be recoverable.References:
This loss of neuron function and motor control is responsible for slowness of movement (Bradykinesia), rigidity, postural instability, reduced movement amplitude (Hypokinesia) and difficulty in swallowing (Dysphagia). The mechanism for the brain to control muscles begins to fail. When the neurons connecting the substantia nigra to the striatum fail or die, cutting off a critical dopamine source, the result is that there is too little dopamine and one has difficulty initiating movement. Another brain pathway affected by Parkinson's occurs with interneurons which enable local communication within the striatum.
Description of Parkinson's and the participation of Alpha-synuclein and Lewy bodies
The most common symptom of Parkinson's disease are the tremors which most typically occur in a leg, arm or jaw. The tremors are caused by a feedback loop which puts the neurons in control of motion in the Substantia Nigra, controlled by the cerebellum and cerebral cortex which controls coordination and voluntary movements respectively, to be challenged by the part of the brain responsible for self awareness (thalamus and subthalamic nucleus) as to where the limbs are located. The failure to flow proper quantities of dopamine also causes a failure to control and locate the limb properly and a failure to properly sense its location.
Drugs targeting Parkinson's disease improve one's condition by providing a dopamine precursor used by the brain to develop more dopamine to make up for the lack of dopamine caused by the loss of dopaminergic neurons. Note that these treatments are not a cure, don't slow down the progression of Parkinson's and often have permanent long term side effects.
Parkinson's has known genetic mutations associated with the disease but 75% of the cases have no known cause and this is known as idiopathic or sporatic Parkinson's disease. It is thought that idiopathic Parkinson's disease is caused by environmental pathogens and is thus a unique disease to that individual in cause, rate of progression and motor disruption symptoms. Parkinson's disease is not a single illness with a single set of symptoms. When Parkinson's afflicts those under the age of 50, it is known as Young Onset Parkinson's Disease or YOPD.
Parkinson's strikes men 40% more often than women but men are more exposed to toxins through the workplace as men make up 75% of the farmers (pesticide and herbicide exposure), 90% of chemical workers, 96% of welders (manganese exposure), 97% of pest control workers (pesticide exposure) and 80% of metals and plastic laborers. The usage of chemicals, pesticide and herbicide worldwide have grown repidly and so has the prevelence of Parkinson's disease with the age adjusted rate for Parkinson's worldwide up 22%, India up 30% and China up by 116% over the last 25 years (ref). On the other hand, The Netherlands has banned paraquat and other pesticides linked to Parkinson's and saw that the number of incidences of Parkinson's decreased dramatically (1990-2011 ref).
Due to the growth in the use and generation of neurotoxic chemicals, the global burden of Parkinson's disease has doubled since 1990 (1990-2016: ref) and is expected to double again by 2040.
Diagnosis is usually given by a neurologist who observes behavior and movement. Definitive diagnosis can be done with a DaTscan which can visualize the brain’s dopamine. The DaTscan requires the injection of a radioactive agent into the blood stream many hours before the scan is performed. The higher the number of healthy cells having dopamine, the brighter the images. The DaTscan can distinguish the cause of tremors as being the result of Parkinson's disease or of another movement disorder such as essential tremor or drug-induced parkinsonism.
Computed Tomography (CT) scans of people with Parkinson's will appear normal but the more advanced single photon emission computed tomography (SPECT) scan can show how blood flows to tissues and organs. A SPECT scan combines CT with a radioactive tracer. The tracer emits gamma rays that can be detected by the CT scanner. Radioisotopes used in SPECT scans are typically iodine-123, technetium-99m, xenon-133, thallium-201, and fluorine-18. SPECT scans differ from positron emission tomography (PET) scans in that the tracer remains in the blood stream thus imaging areas of blood flow rather than being absorbed by surrounding tissues.
There are drug treatments and even some surgical treatments which address symptoms, but currently there is nothing approved by the medical community to stop the progression of Parkinson's or to reverse the damage done.
One can remove neurotoxic sources by eating organic meals to avoid neurotoxic pesticides and herbicides, eliminating mold toxins (or moving to a mold free environment), replace mercury amalgam fillings, etc. There are detoxification supplements and protocols as well as chelation therapies for the various toxins, to cleanse the body and mind. There are improvements one can make to their diet, duration of food consumption, probiotics and exercise and physical therapy which can help to resist the decline as much as possible. Some have been successful reversing their ailments substantially by restoring damaged but not dead motor neurons. This outcome is more likely with those who have been newly diagnosed and have some motor neurons that can be saved. Growing new replacement neurons is a tougher path and is that taken by stem cell researchers in the hope for a future treatment.
Upon receiving a diagnosis of Parkinson's disease one can take the following steps:
This website outlines steps one can take to help their condition.