From the Guidelines
Parkinson's disease is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra, leading to a significant reduction in dopamine levels in the basal ganglia, particularly in the striatum, and resulting in the hallmark pathological finding of Lewy bodies containing alpha-synuclein 1. The pathophysiology of Parkinson's disease (PD) involves a complex interplay of neuronal loss, protein aggregation, and neurotransmitter imbalance. The degeneration of dopamine-producing neurons in the substantia nigra leads to a significant reduction in dopamine levels in the basal ganglia, particularly in the striatum. This reduction in dopamine levels disrupts the normal balance between excitatory and inhibitory pathways in the basal ganglia, resulting in the classic motor symptoms of Parkinson's: bradykinesia, rigidity, resting tremor, and postural instability 1.
Some key features of the disease include:
- Progressive degeneration of dopaminergic neurons in the substantia nigra
- Reduction in dopamine levels in the basal ganglia, particularly in the striatum
- Presence of Lewy bodies, abnormal protein aggregates containing alpha-synuclein
- Disruption of the normal balance between excitatory and inhibitory pathways in the basal ganglia
- Classic motor symptoms: bradykinesia, rigidity, resting tremor, and postural instability
- Non-motor symptoms: depression, cognitive impairment, and autonomic dysfunction
The disease process typically begins years before clinical symptoms appear, with approximately 40-50% of dopaminergic neurons already lost by the time of diagnosis 1. While the exact cause remains unclear in most cases, both genetic factors and environmental factors contribute to the disease. The pathology also extends beyond the dopaminergic system to affect other neurotransmitters, explaining the diverse non-motor symptoms that often accompany the disease 1.
From the Research
Pathophysiology of Parkinson's Disease
The pathophysiology of Parkinson's disease (PD) is a complex process involving multiple factors and brain regions. Key aspects include:
- Progressive loss of dopaminergic neurons and decreased dopamine content in the substantia nigra pars compacta 2
- Disturbances in dopamine synthesis, storage, transportation, and metabolism contributing to neurodegeneration of dopaminergic neurons 2
- Interaction between dopamine and environmental and genetic factors in PD pathophysiology 2
Role of Basal Ganglia
The basal ganglia play a crucial role in the pathophysiology of PD, with:
- Dopamine depletion shifting the basal ganglia toward inhibiting cortically generated movements 3
- Imbalance in the direct and indirect pathways of the basal ganglia leading to motor complications 3
- Involvement of dopamine loss in extrastriatal basal ganglia nuclei, including the globus pallidus and subthalamic nucleus, in PD pathophysiology 4
Clinical Features and Pathophysiology
The clinical features of PD, such as motor symptoms and cognitive deficits, are related to the underlying pathophysiology, including:
- Loss of dopaminergic neurons in the substantia nigra and resulting dopamine depletion in the striatum 5
- Dysorganisation of basal ganglia circuits and disturbed subcortico-cortical interactions 5
- Abnormal synchronous oscillating neuronal activity within the basal ganglia-thalamo-cortical loops contributing to parkinsonian symptoms 6