Parkinson's, Alzheimer's, ADD and Other Neurodegenerative Disorders

Paul L. Reller L.Ac. / Last Updated: August 03, 2017


The history of the causes of increases in incidence of Parkinson's, Alzheimer's and other neurodegenerative diseases and syndromes

In the 1950s the food industry stripped vegetable oils of Omega-3 fatty acids to extend the shelf life on products and allow for more success in corporate food production. Transfats were used instead, such as margarine and shortening, and a dramatic increase in incidence of Parkinson's and other neurodegenerative disorders occurred, as scientists link an imbalance of essential fatty acids to neurodegenerative pathology. Essential fatty acid balance is a key aspect to immune function and physiological ability to clear excess oxidative free radicals and repair unhealthy tissues. This isn't the complete answer to the cause of neurodegeneration, but it is a piece of the puzzle. As mentioned above, commercial food production also produced advanced glycation endproducts (AGEs), which produced dysfunction in a different way. At the same time, our country expanded energy production dramatically, mostly with coal fired power plants that spew tons of organic lead and mercury molecules into the air, which enters our lungs, and becomes part of the food and water supply. These heavy metal contaminants accumulate in our brain tissues and eventually cause many problems with neural firing and oxidative clearing (a complete article on lead, mercury and heavy metal pollution is also available on this website). The widely used herbicide paraquat and other pesticides and herbicides have also been implicated in neurotoxicity and Parkinson's disease. Added to these causative factors is the link between the widely prescribed proton pump inhibitors to treat gastric acid and GERD and significantly higher risk of developing a neurodegenerative disorder. A 2016 study printed in JAMA Neurology revealed that a large German cohort study showed a 42-52 percent increased risk for developing neurodegenerative disease with chronic use of the drugs. These combinations of unhealthy and poorly regulated environmental toxicities and harmful products of industrial food production, along with a polypharmacy approach to health problems rather than integration of restorative medicine to actually fix the problem, are at the root of the explosion of neurodegenerative diseases in the modern population.

In 2012, a study at Columbia University in New York, headed by Dr. Nikolaos Scarmeas MD, and published in the online medical journal Neurology, confirmed that sufficient levels of omega-3 fatty acids in the diet, such as EPA and DHA, was the most significant nutrient dietary factor associated with lower levels of beta-amyloid proteins AB40 and AB42 in blood plasma, which is linked to plaque accumulation in the brain and Alzheimer's neurodegeneration. Previous study of diet and neurodegeneration by this research team had indicated that populations that ate a so-called Mediterranean-type diet, with an array and balance of healthy fats, showed a decreased risk of neurodegenerative disease and cognitive impairment (dementia). This further study showed that the decrease in omega-3 fatty acids in the modern diet, a consequence of the modern processing of common vegetable oils to achieve longer shelf-life of processed foods, was directly responsible for increased levels of beta-amyloid, the so-called "sticky protein", which is the key component of neurodegenerative "tangles" associated with Alzheimer's disease. The study group also reviewed levels of saturated fats, monounsaturated fats, omega-6 fatty acids, folate, beta-carotene, and the vitamins C, D, E and B12, to see if these affected the levels of circulating beta-amyloid. None of these nutrients showed a significant relationship to the problematic types of beta-amyloid proteins in blood plasma. This analysis (a study review is available below in additional information) confirms that the change in the content of fatty acids in processed vegetable oils and transfats is responsible for a key factor of neurodegenerative disease, the increase in problematic types of beta-amyloid "sticky proteins" in circulation contributing to the gradual formation of beta-amyloid plaques in the brain, the hallmark of Alzheimer"s disease. This analysis does not rule out the other contributing factors to the disease, but does confirm what many experts have surmised is a key public health factor that has led to the extreme rise in neurodegenerative disease in the United States.

Today, more than 5% of people over 75 are diagnosed with some type of serious neurodegenerative disorder, and as far back as 1989 studies by Brigham and Women's Hospital in Boston, published in the Journal of the American Medical Society, stated that an estimated 10.3% of the population over 65 years of age had probable Alzheimer's disease (JAMA 1989 Nov 10;262(18):2551-6). Less serious neurodegenerative disorders, such as attention deficit and hyperactivity disorder, affect an even greater percentage of the population, even our children. These numbers are growing and do not even reflect the undiagnosed population who are just thought to be suffering from the effects of aging, called mild cognitive dysfunction clinically, and cynically called senility in the past. Incidence of neurodegeneration are not just limited to the elderly population, as new research uncovers the pathophysiology of Attention Deficit and Hyperactivity Disorder, and this disease too shows that measurable neurodegeneration is occurring, even in children. Early stages of serious neurodegenerative disorder may be without symptoms for many years, and treatment at the endstage may only accomplish a slowing or stopping of the neurodegeneration that causes symptoms at this stage. The aging baby boomer population, and indeed all of us, need to understand that there is a need to act now, both to prevent and reverse one's own neurodegeneration, but also to act now to get our government to address the causes of neurodegenerative diseases in our country.

To counter the awareness of environmental causes of neurodegenerative disorders and subsequent alarm by the public, many articles and research studies were engendered by industry funding espousing a genetic link to these disorders, rather than an environmental cause. So far, scientific study has found only rare links to potentially inherited Parkinson's and Alzheimer's. A mutation of the LRRK2 gene called PARK8 was found in only 5% of the Parkinson's population, showing little causative genetic link in reality. The public needs to be diligent to get our government to clean up heavy metal toxicities and to regulate the food industry to prevent these types of neurodegenerative health problems for future generations. The real causes of these neurodegenerative pathologies are not genetic, but a combination of public health issues, industrial food production, environmental toxins, overuse of antibiotics, immunodeficiency, and lifestyle stress. Unless we become educated to this complex problem and act now, the population of the United States is going to face ever increasing problems with these neurodegenerative diseases. Since the cost of care of these patients, and the loss of productivity, is enormous, this health problem affects not only the patients, but all of us, especially when the cost of health care and social spending has already spiraled out of control.

What are the causes or contributors to attention deficit and hyperactivity at an early age? ADHD has also proven to be a neurodegenerative condition, even at an early age. We all know by now of the growing problem of hyperactivity in children and the treatment with the dopamine reuptake inhibitor Ritalin that is also used to treat adult ADHD. Clinical blinded placebo trials have shown that such chemicals as artificial food coloring and sulfite and benzoate preservatives have increased hyperactivity in children diagnosed with the disorder. See:'%20behavior_Itaya.pdf. How do benzoate preservatives and artificial food dyes contribute to neurodegenerative pathology? Once again, the answer is complicated, but a few key points elucidate the basic process. Read on.

Benzoic acid, a common food preservative, has been demonstrated to cause oxidative stress. These preservative acids also have a negative consequence on cellular membranes, that both act to insure effective metabolism at dopamine receptors, and to protect the cell from environmental cytotoxins that enter the bloodstream. Cell membranes protect the mitochondria in our brain cells, the small oxygen factories that supply energy to our cells, and which are the subject of much study of the root of neurodegeneration. While organic food preservative acids, such as benzoic and sorbic acid, are stable, or cytostatic, under conditions used for food preservation, they may cause a disruption of the cellular plasma membrane and cause a cytocidal effect when they reach our brain, especially under acidic conditions in the body. Acidity in the body is increased when there is too much intake of simple carbohydrates like sugar, refined grain, beer, granola, etc. Periods of high body acidity may also occur with poor stomach function, or poor hormonal regulation of key antacids, such as calcium. High body acidity may make benzoic acid food presersetives toxic and damaging to our brain cells.

High intake of benzoic acid preservative, coupled with a lack of healthy fats, or lipids, that make up the phospholipid membranes, and with a deficiency of oxidative potential to clear the damage, results in neurodegenerative cell death and functional cell membrane disruption that may occur at an early age. As mentioned, advanced glycation endproducts (AGEs) are also a dietary and metabolic problem that affects healthy cell membranes. When children eat too much processed food with these ingredients, it is easy to understand how the health of their brain cells are damaged. The problem in children is probably easily reversed by sticking to a healthy diet that avoids preservatives and food dyes, transfats, and simple carbohydrates, and includes sufficient antioxidant foods and omega-3 fatty acids. Even parents that believe that they are keeping their children's diet healthy are sometimes mistaken, as large intake of fructose, in the form of fruit juices and supposedly healthy carbonate beverages, can create an excess of AGEs. Over time, without ingredients for cellular repair, such as antioxidants, essential fatty acids, attention deficit and hyperacitivity disorder may become chronic. All scientific studies of neurodegeneration now demonstrate a measurable decrease in tissue quantity in key areas of the brain that are the result of this type of cellular damage, utilizing newer functional MRI imaging. This objective data is irrefutable.

All of the above causes of neurodegeneration leave our bodies more susceptible to inflammatory degeneration. Most studies of neurodegenerative disorders now focus on excess inflammatory processes and lack of oxidative clearance as the prime problem in neurodegeneration. Studies show that increased exposure to viral illnesses, and the penetration of some strains of these viruses deep into the organ tissues, generates excessive lipopolysaccharides that are released from antigen cell walls, and increase pro-inflammatory cytokines such as interleukin-1 (IL-1) and TNF-alpha. The chronic increases in expression of IL-1 has been shown to have both direct and indirect mechanisms that exacerbate neurodegeneration of dopaminergic neurons as well. IL-1 directly triggers 6-OHDA-triggered dopaminergic toxicity, and increases oxidative stress. Lipopolysaccharides were found to directly accelerate and increase motor signs in study animals, showing a positive link to direct hyperactivity cause. Some of the new pharmaceutical utilized (e.g. Enbrel) inhibit the cytokine TNF-alpha to reduce symptoms. These same effects, inhibition or modulation of inflammatory ctyokines, are proven to be achieved efficiently with herbal medicine. We can't completely eliminate viral illness from our world, but we can work to create a healthier response to viral illnesses in our bodies. Complementary Medicine has many therapeutic tools to enhance the immune system as well as directly help in inhibiting the harmful imbalances of inflammatory mediators. Scientific study allows the TCM physician to better utilize these herbal chemicals and specific acupuncture stimulations to achieve these goals.

In summary, the known history of causes of increased incidence of neurodegenerative disorders in the United States population include unhealthy ingredients in commercial processed foods that go unregulated, increasing amounts of lead, mercury and other heavy metal organic compounds, primarily from dirty coal fired power plants that go unregulated, and the increased oxidative stress and decreased immune health generated by our modern lifestyle, diet, and environment. Hormonal imbalance has also proven to play a significant role in mitochondrial dysfunction and neurodegeneration. As individuals, and as a population, we can change these harmful aspects of our world now, and clean up both our own bodies, and the environment. By utilizing Complementary Medicine, understanding and improving our habits, and urging our politicians to act now, future generations as well as our own will benefit immensely.

The continuing debate over causes of Neurodegenerative Disorders and the approach to treatment

To date we still have strong debate about the very nature of Parkinson's, with researchers arguing over the location of the origin of the disease in the central or peripheral nervous system. There is also strong debate continuing over the location of the metabolic and neural oscillations that trigger the tremors and disrupt the cognitive processes, with some arguing that the origins lie within the cells, and others arguing that the neuronal network is responsible. Standard therapeutic approaches with pharmaceutical agents continue to be disappointing, and remain focused on increasing dopamine purely for lack of a better strategy, and despite the fact that we now know that even the dopamine deficiency is related to an imbalance of dopamine stimulation at various receptors, rather than a simple matter of poor dopamine availability. One thing is for certain. This disease is a neurodegenerative disorder that demands a multifaceted and holistic approach in treatment. Research into Parkinsonism has also provided us with a wealth of knowledge and treatment strategy for all of the other neurodegenerative disorders. There is no single pill that will reverse neurodegeneration, which is a complicated multifactored disease mechanism.

At the same time, much research has supported a variety of key strategies for both relieving symptoms and reversing the neurodegenerative aspects of Parkinson's, as well as Alzheimer's, Attention Deficit Disorder, and other neurodegenerative diseases. We now know that even glaucoma is a neurodegenerative disease. Complementary Medicine must play a key role in these treatment strategies. These include stimulation and bioavailability of dopamine in the central nervous system, coupled with replenishment of endocannabinoids and cholines, which are needed to restore a balance in the regulating cells of the substantia nigra, caudate and putamen striatum of the basal ganglia, to help control the tremors and loss of motor control. Restoration of healthy cellular function is also a key, especially health of the mitochondria, or oxidative energy-producing parts of the cells, which contain the key protein enzymes of the fatty acid oxidation and citric acid cycle. Antioxidant therapy and balance of essential fatty acids, with increase in Omega-3 DHA and EPA are also keys to neuroprotective strategies. Recent research has focused on adrenal stress and chronic overstimulation of neuroreceptors as a key aspect of the overall pathophysiology. Here too, acupuncture and herbal medicine can play a key role in improving the treatment outcome. Acupuncture, or TCM, utilizes a combination of therapeutic protocols based on sound scientific evidence. The licensed Acupuncturist may be skilled and knowledgeable with nutrient therapy, herbal medicine, needle stimulation, and lifestyle advice. This combination is very important when treating or preventing neurodegeneration. Neurodegenerative disease, because of its complex nature, requires a thorough, comprehensive, and persistent treatment approach. Anything less is doomed to failure.

Neurodegeneration usually occurs over time, and the causes are usually multifaceted. Chemical causes are the chief concern, but hormonal imbalance, effects of aging, physiological stress, and a genetic or epigenetic inherited propensity to neurodegeneration are also important concerns. In recent years, theories of a systemic bacterial endotoxicity (see the article on this subject on this website) creating an inflammatory response, has been added to the factors that may cause neurodegeneration and Parkinsonism. Overuse of antibiotics and creation of many antibiotic-resistant strains of bacteria may have contributed to endotoxicity. These disorders present both a public health threat that should be addressed by our government, as well as an individual threat, that should be addressed by the physician most important in the treatment team, you. The individual must take a more proactive approach to prevent or treat neurodegenerative disorders. The complexity of the problem should not deter the individual from taking decisive action, and the Complementary Medicine physician is ideal to integrate into this treatment and prevention strategy at any level. Food additives, preservatives, unhealthy diets, environmental toxins, especially heavy metal toxins, adrenal stress, oxidant stress, fatty acid imbalance, endocrine disorder, especially melatonin dysregulation (e.g. workers on the night shift, or airline attendants), chronic inflammatory states, and advanced glycation endproducts (e.g. patients with obesity, metabolic syndrome, or atherosclerosis) are all significant factors implicated in the pathology of neurodegeneration. This array of causes and contributors is now supported by sound research. Some other important causes are still less well known.

Neurodegeneration and mitochondrial dysfunction may also be a result of iron overload toxicity. Iron is an important metal ion in our body and the levels of iron are usually tightly controlled. Since iron is highly reactive as an oxidative agent, normally up to 70 percent of our iron is bound to the ferritin or transferrin proteins, or other transport and storage proteins, where it cannot participate in oxidative reactions. The fact that it is able to oxidize quickly (as in rusting outside of the body) makes it an ideal carrier of oxygen in our red blood cells. When the neutralizing capacity of these storage and carrier proteins is exceeded, excess iron binds weakly to other proteins in the blood and cells, where it participates in oxidative reactions and peroxidation of cellular components, or organelles, such as mitochondria, lysosomes, and sarcoplastic membranes (integral to nerve conduction). Iron overload toxicity is not uncommon, but is only looked for in diagnosis when it becomes very serious, resulting in heart disease, dysfunctions of the pancreas or liver, or gonadal dysfunction and infertility. Patients with thalassemia, sickle cell anemia, hepatitis, cirrhosis, chronic inflammatory conditions (e.g. autoimmune disorders with rheumatic disease and positive rheumatoid factor), infections, alcoholism, repeated transfusions, or even in patients that take too many iron supplements, or eat an unusual excess of red meat, may have a history of iron overload toxicity. If the iron in our bodies is not handled by the appropriate metabolism of transport and storage, gradual accumulation in tissues may lead to a neurodegenerative condition, and iron chelation may have a positive effect.

An array of food additives called excitotoxins, such as hydrolyzed vegetable protein, aspartame, and MSG, are also the subject of much research into neurodegenerative pathology and central nervous system (CNS) dysfunctions that may lead to neurodegenerative states. A growing body of sound research has linked these food additives to a wide array of neurological problems, including Parkinson's disease, Alzheimer's disease, Huntington's disease, ALS, learning disorders (ADD), developmental disorders, neuropsychiatric disorders, dementia, and even obesity, migraines, seizure disorders, certain endocrine disorders, and CNS problems in chronic aftereffects of Lyme's Disease. These food additives are now present in almost all processed foods. Since scientists discovered health risks associated with MSG additives in the 1970s (MSG is a natural glutamate compound that enhances neurochemical systems related to attraction and enjoyment of food), the food industry did not heed public health warnings, but instead developed a vast array of glutamate compounds, called excitotoxins, that increase our desire to buy their products.

Today, MSG-like excitotoxins are disguised as "natural flavorings", soy protein extract, textured protein, yeast extract, hydrolyzed vegetable protein, and artificial sweeteners such as aspartame (read below to gain a better understanding of aspartame). These altered glutamate molecules accumulate in the brain and cause neural dysfunction over time, as the amino acid glutamate is a key basic building block of many important regulatory chemicals in our brain, as well as itself being a neurotransmitter. Since glutamate is tightly controlled in the brain, and is normally kept at very small concentrations in extracellular fluid, these altered glutamate compounds begin to overload neural firing as they accumulate. The main drug used to treat Parkinson's disorders is L-Dopa, or synthetic dopamine, which itself is a weak excitotoxin that has now been proven to actually accelerate Parkinson's neurodegeneration with chronic use. At first, L-Dopa may relieve symptoms, but in time these symptoms will worsen in an accelerated fashion. The public needs to start expressing outrage that our food industry treats food chemistry with such a cavalier attitude, and demand that the commercial food industry hire public health experts to guide what they put into our food. Surely, we could have processed foods that improve our health rather than destroy it.

Studies investigating the role of bacterial endotoxins in neurodegenerative pathology have turned up some surprising evidence of a multifactorial component to Parkinson's disease. Researchers at Texas Christian University, in 2007 (cited below), found that a combination of inflammatory bacterial endotoxin lipopolysaccharide (LPS) promoted significant dopamine depletion and neurological impairment only when combined with a neurotoxin (MPTP). Such research shows that the various environmental toxicities linked to neurodegeration may only cause significant disease symptoms when combined. To date, research into studying these multifactorial causes has constituted only a small portion of the research. This is because research today is dominated by a need to produce a single allopathic pharmaceutical, and is not centered on purely finding the true array of causes of disease, sort of the quantum field of symbiotic causative factors. The neurotoxin studied, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), has been proven to cause permanent symptoms of Parkinsonism, and so has been utilized as a study model. MPTP may be produced during the manufacture of street narcotics that include MPPP, a synthetic opioid, and the investigation into these drugs led to the discovery of the neurotoxicity of MPTP. MPTP by itself, though, cannot cause neurotoxicity, and the subjects affected by this chemical apparently had other symbiotic factors that caused the neurotoxicity. The search for these symbiotic factors has led to many interesting findings in the etiopathology of Parkinson's. Such research confirms that an array of factors must work together to cause severe disease. Chronic inflammatory pathways, reactive oxygen species, and chemical neurotoxins in the environment are the most likely trio of causes that work synergistically to cause neurodegeneration in most subjects.

Metabolic dysfunctions and their relationship to Alzheimer's

Researchers have uncovered a variety of metabolic imbalances contributing to the progression of Alzheimer's neurodegeneration. In 2007, researchers at Northwestern University published findings that showed that insulin resistance was a key component of neurological dysfunction. The protein called amyloid beta-derived diffusable ligand (ADDL) appeared responsible for the progression of Alzheimer's dysfunction from synapse to synapse, spreading across the brain, and one effect of this neurotoxicity was the depletion of insulin receptors from neurons. Key research widely accepted by health organizations involved with Alzheimer's disease indicates that levels of brain insulin and insulin receptors on affected cells are lower in Alzheimer's patients, and the level of this insulin and insulin receptor deficiency is a marker of the progression of the disease. Insulin is a hormone in the body with complex effects at a wide array of receptor types. In the brain, insulin does not regulate sugar and energy usage so much, but is integral to development, tissue growth and maintenance, memory and learning (see my article on this website entitled Insulin Use and Support Therapies to gain a better understanding). The binding of ADDLs to brain synapses prevents the accumulation of insulin receptors at these synapses, contributing to poor cellular maintenance and repair. Increased insulin receptors express inside the cell, not on the membrane, decreasing the usage and need for insulin. These researchers at Northwestern University, William L. Klein, professor of neurobiology in the Weinberg College of Arts and Sciences, and Fernanda G. DeFelice, from the Federal University of Rio de Janeiro, found that neurons affected by ADDL showed a virtual abscence of insulin receptors on the dendrites of the neuron, or the branched projections of nerve cells that conduct the electrochemical signals. Dendrites with an abundance of insulin receptors showed no ADDL binding. Clearly, both dysfunction with insulin metabolism and the accumulation of advanced glycation endproducts, such as beta-amyloid, are integral to this aspect of the disease.

The pharmaceutical industry has responded to this research on insulin receptor deficiency by creating aerosol insulin medication to improve the symptoms with alzheimer's disease. Unfortunately, while a dosage of insulin released into the nasal passages may temporarily help alleviate symptoms, this will not correct the problems with insulin receptor deficiencies. The clearing of amyloid-beta diffusable ligands (ADDLs) is clearly an important goal in treatment. A more complex strategy to correct these metabolic problems and restore neural cell functions, clear misshapen protein accumulations, and block the formation of advanced glycation endproducts (AGEs) is needed.

These findings of the ADDL accumulation and effects on neuron maintenance, with decrease in insulin receptors on the membranes of affected cells and the subsequent decrease in insulin effects, explains why there is an unclear association with overall beta-amyloid plaque burden and cognitive defects in all cases. It is probably not just the accumulation of the advanced glycation endproduct plaques that is important, but the accumulation of specific variations on these problematic protein, fat and sugar molecules. These ADDLs, or amyloid beta-derived diffusable ligands, are oligomers of amyloid beta molecules. A number of oligomers, or molecules that consist of just a few atoms or small molecules (monomers) that bind easily to form larger polymers, of beta-amyloid protein complexes, are found to be integral to the Alzheimer's pathology. The most common natural monomer is glucose. A ligand is a small molecule that easily forms a complex with a biomolecule, and serves to increase the signal, or trigger, increased binding to a site on a target protein. Metabolic dysfunction is seen as the origin of these ligands of beta-amyloid protein, fat and sugar complexes.

Metabolic Syndrome, typically still called diabetes type 2, and Alzheimer's disease have signs of increased oxidative stress and accumulation of advanced glycation endproducts (AGEs) in common. Patients with Metabolic Syndrome, or diabetes type 2, appear to have an increased risk for Alzheimer's disease, primarily because these AGEs accumulate in neurofibrillary tangles and amyloid plaques. A sequence of studies have demonstrated the importance of this pathological mechanism. The Rotterdam study followed over 6000 elderly patients for a number of years and determined that insulin resitance and Metabolic Syndrome, called type 2 diabetes, doubled the risk of the patient acquiring a neurodegenerative disease. Patients taking synthetic insulin showed 4 times the risk. A high incidence of diabetes and Metabolic Syndrome now exists in our aging community, and just the maintenance of blood sugar and total cholesterol with drugs such as synthetic insulin has not decreased the potential for these health dysfunctions to result in neurodegenerative states. In fact, these studies show that the risk is perhaps increased with the use of the synthetic insulin, statin drugs, etc. The term diabetes type 3 was coined in 2005 to define Alzheimer's disease by Dr. Suzanne de la Monte, a neuropathologist at Brown University, when her research on postmortem brain tissue of Alzheimer's patients found that Alzheimer's disease may be defined as a neuroendocrine disease associated with insulin signaling defects. Her research showed that a reduced insulin, insulin-like growth factor, and insulin receptors on the outer parts of neurons, reduced the regulatory tau protein, and ultimately led to cell death. While introduction of synthetic insulin produces immediate improvement in glucose utilization in the brain, memory, and cognitive abilities, long-term use may be problematic, as the Rotterdam study indicated. The restoration of the insulin metabolism, correction of Metabolic Syndrome, inhibition of advanced glycation endproducts (AGEs), and improved neuroendocrine balance, all of which can be accomplished with Complementary Medicine, provides a safe and effective therapeutic protocol to patients.

Another aspect of metabolic dysfunction occurs when regulatory proteins, which are often large molecules, do not fold and unfold properly. The synuclein family of proteins are primarily expressed in neural tissues, and alpha-synuclein has been the focus of much research in Parkinson's since it was found that several families with an inherited autosomal dominant form of the diseases expressed mutated alpha-synuclein. This research has since discovered that alpha-synuclein that fails to fold and unfold properly may lie at the heart of the pathology, contributing to protein aggregation and cell membrane instability. An alpha-synuclein fragment known as the non-Abeta component of amyloid also is found in the amyloid-beta plaques in Alzheimer's. Protein homeostasis involves a complex array of chemicals that control protein folding and unfolding, and when this cycle is dysfunctional, glycosylated proteins may not transported correctly, and advanced glycosylation endproducts (AGEs) may accumulate. Coupled to this are dysfunctions of endoplasmic reticulum-associated degradation (ERAD), leading to alpha-synuclein proteins that do not unfold, and are not transported to the cytosol of cells for degradation. Homeostasis of this protein metabolism is potentially a key to these neurodegenerative pathologies. Research is ongoing to reduce protein aggregation, enhance protein folding, restore protein homeostasis, and stabilize misfolding-prone proteins. Glycosylation is a fundamental part of the endoplastic reticulum's protein quality control, and insuring that this process works is thus very important, as are effort to reduce ER stress. Novel therapeutics to aid in this protocol are nutritional agents to clear excess lectins, plant flavonoids (especially methoxyflavonoids), quercetin, genistein, and formulas to help clear excess AGEs.