The reason why an individual gets Parkinson’s disease has not yet been fully understood. That the causes responsible for this pathology seem to be multiple. In this article, we will give you a complete guide about what causes Parkinson’s disease. Furthermore, it should be emphasized that these causes can interact with each other, creating a sort of enhancement that leads to a vicious circle of neuronal dysfunction, atrophy, and, finally, cell death (this is why we speak of a multifactorial hypothesis).
Among the factors involved in the development of Parkinson’s disease, the aspects concerning aging, genetics, the environment, and exogenous toxins, but also viruses, endogenous factors, cell damage, the presence of high quantities of iron, and finally apoptosis (programmed cell death process).
In Parkinson’s disease, the biochemical process mainly responsible for clinical manifestations is reducing a neurotransmitter, dopamine, which is essential for the harmonious execution of movements. That the reduction in dopamine production is due to a massive degeneration of nigral neurons. There is a progressive degeneration of the mesencephalic neurons. The meaning is that as we age. There is a physiological reduction of nigral neurons (400,000 units at birth, 25% reduction at 60 in normal healthy individuals).
These results allowed us to hypothesize that what causes Parkinson’s disease may be caused by an accelerated aging process. However, it is not yet clear how this aging process so selectively affects only the pigmented nuclei of the trunk. It is therefore plausible that age can change the sensitivity of dopaminergic neurons to other factors responsible for the disease, such as acute exogenous insults (occasional toxic, environmental factor, viral agent) or endogenous, such as metabolismcytotoxic catecholaminergic (which uses the so-called “catecholamines, “which are adrenaline, noradrenaline, and dopamine), particularly harmful for some neuronal populations and not for others that use the same neurotransmitter.
What Causes Parkinson’s Disease: Genetics
Looking at genetics instead, about Parkinson’s disease, there is great interest in trying to find out which gene is responsible for the majority of cases of the disease. Studies of homozygous twin pairs were conducted between 1969 and 1983 by several groups of researchers. These independent research results revealed that genetic factors played a weak if not small role in the causes of what causes Parkinson’s disease. In recent years, however, some genealogies have been described in which the disease is transmitted in an autosomal way.
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Environment and Exogenous Toxins
It has also been hypothesized that exposure to some exogenous agents may contribute to the development of Parkinson’s disease. In fact, some studies conducted in the 1980s had observed that drug addicts who took synthetic heroin whose co-product was MPTP (1-methyl-4phenyl-1,2,3,6tetrahydropyridine) developed a parkinsonian syndrome that showed lesions, both anatomically and pathologically, at the substantia nigra level and which responded well to L-DOPA. MPTP is neurotoxic, but in itself, it would be harmless. Once introduced into the body, at the level of the central nervous system, it is taken up by cells which, through the activity of type B monoamine oxidase (MAO-B), metabolize it leading to the production of an active ion, 1methyl-4phenylpyridine or MPP +. So once produced, this ion accumulates within dopaminergic neurons, using the dopamine reuptake system.
Once re-captured, it concentrates at the mitochondria level, where it acts as a selective inhibitor of respiratory complex I (NADH CoQ1 reductase). Following this inhibition, there is a reduction in ATP production and, consequently, a decrease in the efficiency of the Na + / Ca ++ proton pump. Then there is an increase in the intracellular concentration of Ca ++ ions, an increase in oxidative stress due to the increase in electron dispersion in complex I, and an increase in the production of superoxide ions by the mitochondria. All this then consequently leads to cell death.
Type of observation
The interest in this type of observation is very important because it provides the possibility of producing experimental models of what causes Parkinson’s disease in animals. In line with these observations, in fact, the epidemiological data has revealed that those who use these substances. But not the consumers of products treated with these substances fall ill more easily with Parkinson’s disease. By this line of thinking, there is the environmental hypothesis, according to which, following various epidemiological researches conducted on healthy individuals and individuals affected by Parkinson’s disease.
It appeared that Parkinsonians had been more exposed to substances such as herbicides or insecticides, or they had carried out agricultural activities, they had drunk well water, or they had spent most of their lives in rural areas in greater numbers than healthy individuals, considered as the control group. However, recent studies have shown that the only true independent risk factor between Parkinsonian individuals and healthy individuals concerns exposure to herbicides and pesticides.
Furthermore, among the various neurotoxins present, others have been identified as dangerous, including n-hexane and its metabolites, commonly contained in glues, paints, and gasoline. Parkinsonian individuals. Then individuals with Parkinson’s disease who had perhaps led a better lifestyle. It is important to remember that among the environmental toxins. Also, carbon monoxide, manganese, carbon disulfide, and cyanide ions may be responsible for Parkinson’s disease. In this case, however, these toxins target globus pallidus rather than substantia nigra. Globus pallidus is also part of the basal ganglia, which will be discussed in later chapters.
Viruses and Infectious Agents
Alongside the toxins just described, there was also the hypothesis concerning the involvement of viruses responsible for Parkinson’s disease. In fact, in 1917, following the epidemic of lethargic encephalitis of Von Economo. A large number of cases of what causes Parkinson’s disease had been found. However, following the non-determination of the virus and its disappearance in 1935.
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What Causes Parkinson’s Disease: Endogenous factors
On the other hand, the hypothesis of endogenous factors has aroused greater interest. Radicals are highly unstable, reactive, and cytotoxic formations. Our organism produces oxygen free radicals due to normal cellular activities, such as oxidative phosphorylation, catabolism of purine bases, modifications induced by inflammatory processes, and following the catecholamine catabolism, including dopamine.
The free radicals of oxygen include the superoxide anionic radical, hydroperoxyl, hydroxyl, and singlet oxygen. Hydrogen peroxide is reactive towards organic substances but is able to interact with transition metals (iron and copper ), thus generating the more reactive hydroxyl radical. Following their formation, free radicals can bind to any part of any biological molecule due to their high instability. These molecules also include DNA, proteins, and lipid membranes. Therefore free radicals are also able to alter nucleic acids, inactivate structural and functional proteins, and deteriorate permeability. And the membrane pump and transport mechanisms. To overcome the problem induced by free radicals, in physiological conditions, cells have numerous systems, enzymatic and non-enzymatic, capable of hindering the side effects of free radicals. However, when the balance between the defense mechanisms and the factors.
What causes Parkinson’s disease endogenous factors definition
Due to the high consumption of oxygen and the high content of oxidizable substrates ( polyunsaturated fatty acids), metal ions (which increase radical reactions), and catecholamines. As described in the first part, the neurons of the substantianigra or substantianigra are rich in dopamine. It should also be added that the brain’s antioxidant defenses are weak; in fact, there is a low concentration of glutathione (which has antioxidant properties ) and vitamin E, and moreover. There is an almost absence of catalase (enzyme belonging to the class of oxidoreductases, involved in the detoxification of the cell from reactive oxygen species). Therefore, these toxic lesions can accelerate the progressive loss of dopaminergic neurons at the nigra level.
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Despite the framework provided by the free radical theory. Among these, we recall cellular damage, which is based on dysfunction at the mitochondria level. In particular, at the level of the respiratory complex I. Some studies have shown that the respiratory chain activity in the brain of an individual suffering from the disease Parkinson’s showed a 37% reduction in the activity of complex I, leaving the activities of complex II, III, and IV unchanged.
What Causes Parkinson’s Disease: Apoptosis
Last but not least, the phenomenon of apoptosis or programmed cell death is also counted among the possible causes of Parkinson’s disease. Cells – based on the signals coming from the surrounding environment – can control apoptotic processes. The exposure of neurons to particular exogenous or endogenous mediators can therefore influence. The cellular control of apoptosis, inducing its activation and thus causing neuronal death. It has recently been hypothesized that dopamine and/or its metabolites may play a role in the pathogenesis of Parkinson’s disease as they seem capable of inducing inadequate activation of programmed cell death.
Stages of Parkinson’s disease
Parkinson’s disease is a neurodegenerative disorder, progressive, insidious, mainly characterized by two phases: a perisintomatica phase and asymptomatic phase. Although it is not yet clear when this phase begins, nor what percentage the loss of dopaminergic neurons is quantified. Parkinson’s based on various research studies, some theories have been formulated. According to which five years would pass between the initial depletion of dopaminergic neurons and the appearance of the first symptoms.
Another current of thought argues that the loss of neurons may begin. As early as forty years before the onset of the disease. Unfortunately, it is very difficult to determine the exact first symptoms on the part of the individual since the onset is gradual and insidious. In fact, some symptoms are so mild that a clinical evaluation is not possible. While signs such as depression or seborrheic dermatitis, which are not motor symptoms, may appear long before motor dysfunction.
However, we can classify the symptomatic phase of Parkinson’s disease into two parts: the early phase and the late phase. Which appears when approximately 70% of the dopaminergic neurons of the substantia nigra have been lost. The second phase, on the other hand, refers to the period in which the disease progresses.
We talk about mild and unilateral involvement. Stage I is characterized by the appearance of tremors affecting the upper limbs at rest. About a year earlier, other symptoms may occur, such as prodromal pain or a feeling of pain, upon careful examination of the individual, slight stiffness. There is a slowing of movements and a worsening in repetition. In particular, some alterations such as trembling strokes, difficulty in rounded strokes, and micrographs occur during writing.
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Bilateral involvement with early posture changes. The individual with Parkinson’s disease assumes a fixed posture, in which the trunk, hips, knees, and ankles are slightly flexed. Furthermore, all movements tend to slow down gradually, resulting in the so-called bradykinesia. Patients often experience reactive depression.
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There is a high impairment of gait, moderate generalized inability. And the appearance of a retropulsion or propulsion. It increases the impairment of postural reflexes. There is a significant slowing of walking and an increase in bradykinesia as retropulsion and propulsion begins to induce falls. At this stage, the patient may occasionally need help with some tasks.
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High disability. At this stage, the individual with Parkinson’s disease most needs assistance in carrying out normal daily activities and is no longer able to live alone. In stage four, the patient has frequent falls, and tasks that require fine motor control are difficult or impossible.
Complete disability occurs. Walking is impossible, and the individual with Parkinson’s can no longer maintain an upright position. He is lying on his back and immobile when in bed, with his head slightly bent on the trunk. So, he constantly has his mouth open due to dysphagia and reduced spontaneous swallowing. He struggles to eat and often develops dehydration and cachexia. Furthermore, the situation is more complicated by the danger of infection due to reduced thoracic excursion and the cough reflex’s ineffectiveness due to the neurological bladder and constant bed restraint. This clinical picture refers to an individual with Parkinson’s who has not undergone any drug treatment.