This condition was first described by James Parkinson in 1817. Dopamine and dopamine receptors generally decreases with age. In Parkinson’s disease, aging is associated with an accelerated loss of dopamine and dopamine receptors.
Degenerative changes are observed in the substantia nigra with marked reduction of dopamine in the striatum and substantia nigra.
In the absence of dopamine, there is a decrease in the excitatory output from the direct striatothalamic circuit while there is an increase in the net inhibitory output from the indirect striatothalamic circuit via the sub-thalamic nucleus. Both results in hypokinetic features.
The term Parkinsonism refers to some other conditions that result in symptoms similar to those in Parkinson’s disease. These include certain viral infections and treatment with certain drugs (phenothiazines) which blocks dopamine D2 receptors. Experimental Parkinsonism can be produced by the drug MPTP (methyl-phenyl- tetrahydro-pyridine). MPTP is converted into MPT+ by monoamine oxidase-B (MAO-B). MPT+ is a potent oxidant that is taken up by dopaminergic neurons in the substantia nigra, which then get destroyed. MAO-B inhibitor diprenyl protects against MPT+ induced Parkinsonism.
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The fact that diprenyl slows down the progress of Parkinson’s disease even when there is no apparent exposure to MPTP suggests that Parkinson’s disease may be caused by some MPT+ like metabolite that is endogenously produced in the body.