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The disease is a progressive movement disorder of the extrapyramidal system, which controls and adjusts communication between neurons in the brain and muscles in the human body.
In the United States, the prevalence of Parkinson's Disease is 160 per 100 000 people, though this increases with age, as indicated by the mean onset of 55 years of age. Symptoms usually begin in the upper extremity, and are usually unilateral at onset.
The cause of Parkinson's disease is not known. Geneticists have since 1997 found nine different specific genetic defects, each of which causes the disease in one or a few families with extraordinarily high incidences of the disease, but such families are rare. While a strong inheritance pattern occurs in only a very small percentage of cases, an affected individual is three to four times more likely than an unaffected individual to have a close relative with Parkinson's. Having a parent with Parkinson's raises one's lifetime risk of developing the disorder threefold, from the general population's figure of 2% to about 6%. Genes that have been identified include alpha-synucleinAlpha-synuclein is a normal protein found in the brain. It is predominantly a presynaptic neuronal protein of unknown function, but can also be found in glial cells. Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble, ubiquitin carboxy-terminal hydrolase L1Ubiquitin carboxy-terminal hydrolase L1 UCH-L1 is a deubiqutinating enzyme. A point mutation (I93M) in the gene encoding this protein is implicated as the cause of Parkinson's disease in one kindred. Furthermore, a polymorphism (S18Y) in this gene has bee (UCH-L1), parkinParkin is an E3 ligase in the ubiquitin-proteasome system. Many mutations in parkin have been associated with a familial form of Parkinson's disease termed autosomal recessive juvenile parkinsonism. How loss of function of parkin leads to dopaminergic cel, and DJ-1.
A popular theory holds that the disease might result in most cases from the combination of a subtle genetically determined vulnerability to environmental toxins along with mild exposure to those toxins. The toxins most strongly suspected at present are certain pesticides and industrial metals. MPTP is used as a model for Parkinson's as it can rapidly induce parkinsonian symptoms in patients/animals of any age. Other toxin-based models employ paraquatParaquat is a toxic chemical that is widely used as an herbicide (plant killer), primarily for weed and grass control. In the United States, paraquat is available primarily as a liquid in various strengths. It is classified as “restricted use,” which mean (an herbicide) or rotenoneRotenone ( CAS number 83-79-4) is a colorless-to-red, odorless solid. In solution it is used as a broad-spectrum insecticide that works by inhibiting the transport of electrons in the respiration pathway. It is commonly found in powdered form to treat par (an insecticide).
Minor past episodes of head trauma are also more commonly reported by sufferers than by others in the population. While emotional or a psychological traumaPsychological trauma may accompany physical trauma, or exist independently. Typical causes of psychological trauma are abuse, violence, the threat of either, or the witnessing of either, particularly in childhood. Natural events such as earthquakes and vo can precipitate the initial symptoms or aggravate existing symptoms, this is not the actual cause of the disorder.
The symptoms of Parkinson's disease result from the loss of dopamineDopamine is a neurotransmitter in the brain. As a member of the catecholamine family, dopamine is a precursor to epinephrine ( adrenaline) and norepinephrine ( noradrenaline) in the biosynthetic pathways for these neurotransmitters. Dopamine is synthesize-secreting cells in the pars compacta region of the substantia nigra. These neurons project to the striatum and their loss leads to inhibition of the direct pathway of movement and activation of the indirect pathway of movement. Since the direct pathway facilitates movement and the indirect pathway inhibits movement, the loss of these cells leads to a hypokinetic movement disorder.
Brain cells producing other brain chemicals such as GABA, norepinephrine, serotonin and acetylcholine exhibit minor damage in Parkinson's disease, accounting for some of the wide array of symptoms.
The mechanism by which the brain cells in Parkinson's are lost appears to center on an abnormal accumulation of the protein alpha-synuclein in the damaged cells. This protein forms proteinaceous cytoplasmic inclusions called Lewy bodies . The precise mechanism whereby aggregates of alpha-synuclein damage the cells is not known. The aggregates may be merely a normal reaction by the cells as part of their effort to correct a different, as-yet unknown, insult. It does appear that alpha-synuclein aggregation is enhanced by the presence of dopamine and the byproducts of dopamine production.