Parkinson Disease

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, part of the basal ganglia circuitry controlling motor planning and execution. The substantia nigra projects dopaminergic fibres to the striatum (caudate and putamen) via the nigrostriatal pathway. Dopamine modulates the direct (facilitatory, D1-mediated) and indirect (inhibitory, D2-mediated) basal ganglia pathways that regulate thalamocortical motor output. Loss of dopaminergic input disrupts this balance, resulting in excessive inhibitory output from the globus pallidus internus, suppressing thalamocortical activation and producing the cardinal motor features: bradykinesia (slowness of movement), rigidity (cogwheel or lead-pipe), resting tremor (4-6 Hz pill-rolling, asymmetric), and postural instability (late feature). Intraneuronal Lewy bodies containing misfolded alpha-synuclein are the pathological hallmark. Motor symptoms become clinically apparent when approximately 60-80% of striatal dopamine and 50% of nigral neurons are lost. Non-motor features (hyposmia, REM sleep behaviour disorder, constipation, depression) often precede motor symptoms by years.