The nuts and bolts of Parkinson's Disease.
Parkinson's disease (PD) typically manifests in individuals over the age of 50, with about 5% prevalence in those over 85 years old. Most cases are sporadic with rare inherited variants, suggesting that environmental or toxin-related triggers are likely contributors. PD is characterized by symptoms such as rhythmic tremors in the hands and feet, especially at rest, bradykinesia (slow movement), and akinesia (difficulty initiating movement). These symptoms result from damage and cell death in the brain regions such as the substantia nigra in the brain stem and the locus coeruleus, leading to decreased levels of norepinephrine and dopamine (DA). The substantia nigra projects to the striatum, where DA is the principal neurotransmitter involved in relaying movement messages to the cortex. Neuromelanin, a byproduct formed from the oxidation of DA to quinones and semiquinones and subsequent metal ion binding, is evident in PD due to its black pigmentation. The disease also features Lewy bodies in the substantia nigra and other brain areas, which are composed primarily of the protein alpha-synuclein, abundant in presynaptic neuron terminals. The major treatment for PD is L-DOPA, but excessive DA can lead to the formation of hydrogen peroxide and reactive oxygen species when released into the cytoplasm. This oxidative stress contributes significantly to the neurodegeneration observed in PD