Parkinson’s disease: epigenetics will help in prevention and treatment

You can’t even remember the last time you ate without gagging. You’re sick of your hands shaking. You stop doing most of your normal activities, you fall down a lot when you walk… Is there really nothing you can do about Parkinson’s? Something can! Let’s take a look at what epigenetics research has to offer.

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease. It mainly affects the elderly, but can occur much earlier. Outwardly, it manifests itself primarily by uncontrollable tremors, impaired fine and later gross motor skills, loss of stability and coordination, as well as sleep disturbances and cognitive problems. At the cellular level, it is characterised by the formation of so-called Lewy bodies, which are clumps of alpha-synuclein protein in nerve cells that damage them, and the loss of certain types of neurons.

The exact causes of Parkinson’s disease are unknown. A certain, but not essential, role is played by genetic disposition – in particular, the presence of certain variants of the SNCA gene (which codes for the aforementioned alpha-synuclein protein), PARK2, PINK1, PARK7, LRRK2, VPS35 and CHCHD2. A relatively large role is played by what we call epigenetic influences. These are influences mainly from the external environment (diet, lifestyle, exposure to toxins, etc.) that trigger biochemical reactions in the body that significantly affect the activity of genes in our DNA.

Genes off and on

Importantly, however, scientists have discovered a difference in the expression of a number of genes – i.e. whether they are switched on to produce proteins or switched off. These differences have been found for genes in healthy and affected parts of the brain and between healthy and diseased people.

Large differences were found especially in the SNCA gene. It is advantageous for it to be switched off in terms of disease risk, because then the alpha-synuclein protein, which forms harmful clusters in neurons, is not produced. However, people with Parkinson’s disease have a reduced level of methylation in the so-called promoter of this gene, which means it is more active (switched on). Interestingly, the most commonly used drug, L-dopa, increases the methylation level of this gene.

Other genes, on the other hand, are excessively methylated in Parkinson’s patients, i.e. their activity is reduced, often to the point of complete shutdown. In total, methylation differences have been found in more than 9,900 genes! These processes are closely linked to ageing, which is why the incidence of the disease rises sharply at older ages. In fact, Prof. Horvath, who first coined the term epigenetic clock (expressing the actual age of the organism according to the rate of epigenetic changes), found that epigenetic ageing is accelerated in Parkinson’s patients.

However, the differences between healthy people and Alzheimer’s patients were not only in gene methylation, but also in other epigenetic responses – histone acetylation and regulation by microRNAs. For example, diseased people have significantly reduced levels of microRNA 133b in some parts of the brain.

Avoid toxins

But what causes changes in epigenetic patterns? It is mainly influences from the external environment. Among the most important are substances with toxic effects. For example, research has shown that people with Parkinson’s disease have elevated levels of polychlorinated biphenyls (PCBs) in their brains.

Some toxic substances often found in food also pose a major risk. In particular, some pesticides that are used to protect fruit and vegetables, but are also often found in dairy products, or β-methylamino-L-alanine, which is often found in fish meat.

Drug use may also play a role – for example, the negative epigenetic effects of methamphetamine (meth) have been confirmed.

Interestingly, although smoking is a risk factor for a long list of diseases due to its epigenetic influence, in the case of Parkinson’s disease it may reduce the risk of developing it. The protective effect of caffeine and coffee has also been confirmed – according to research in 2012, coffee drinkers have a 25% lower risk of getting the disease.

Will changing your diet help?

The so-called Mediterranean diet, which is characterised by a high consumption of fish, olive oil, red wine and aromatic herbs – all of which have significant positive epigenetic effects – has been shown to have a positive effect on the development of the disease.

Mixed results were obtained in the case of dairy exposure. Some studies have shown an increased risk with high consumption of milk, cream and ice cream, but others have not. One theory is that dairy products could have a negative effect, particularly in people with lactose intolerance, a problem that increases with age.

Insulin resistance, a condition in which blood sugar levels are high not because of insufficient insulin production but because of reduced tissue sensitivity to the hormone, can also play a role. Neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease, are referred to as type III diabetes. Therefore, it is certainly worth reducing carbohydrate consumption. However, the solution should definitely not be to replace them with artificial sweeteners. Aspartame, for example, can interfere with the transport of certain neurotransmitters and promote brain cell degeneration.

Interestingly, a higher incidence of the disease has also been shown in people who frequently consume canned fruits and vegetables. The cause here may be polychlorinated biphenyls (PCBs), which are often used in the material inside cans. A reaction called lipid peroxidation is probably behind the negative effect of eating fried foods.

Useful dietary supplements

On the other hand, dietary supplements containing substances that combine epigenetic, antioxidant and anti-inflammatory effects can have a significant positive effect.

Omega-3s – two of these fatty acids, DHA and EPA, found mainly in fish oil, have significant epigenetic effects. They have a protective effect on nerve cells, reduce the production of arachidonic acid, which has neurodegenerative effects, promote the production of the growth factor BDNF, which has a positive effect on brain function, and have anti-inflammatory effects.

EGCG – epigallocatechin gallate from green tea has been shown to be effective in both preventing and stopping the progression of Parkinson’s disease. It has extensive epigenetic effects, is highly anti-inflammatory, protects nerve cells and promotes their regeneration, improves cognitive abilities, has significant antioxidant effects, and even directly interferes with the alpha-synuclein protein clumping process.

Curcumin – also a dye found in turmeric root, it prevents the clumping of neuron-damaging proteins and has powerful neuroprotective, antioxidant and anti-inflammatory effects. It also prevents damage to the mitochondria of nerve cells and helps replenish brain dopamine levels in the early stages of the disease.

Resveratrol – another member of the family of plant dyes with epigenetic effects, has significant antioxidant, anti-inflammatory and neuroprotective effects, and also has a positive effect on aging-related processes. When administered to patients with Parkinson’s disease, after just a few weeks, there was a relatively significant improvement in motor and cognitive abilities.