5. Parkinson's Disease Pathology : USMLE Step 1

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Parkinson's Disease Pathology
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Parkinson's Disease (PD) is a progressive neurodegenerative disorder primarily affecting the motor system. The pathology of PD is characterized by the loss of dopaminergic neurons in the substantia nigra, a critical area in the midbrain. This neuronal loss disrupts the balance of neurotransmitters, notably dopamine, leading to the classical motor symptoms of PD: tremors, rigidity, bradykinesia (slowness of movement), and postural instability.

Key Pathological Features:
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Lewy Bodies: The hallmark of PD pathology, these are intracellular inclusions found within the surviving dopaminergic neurons. Lewy bodies are primarily composed of the protein alpha-synuclein, which misfolds and aggregates. This aggregation is toxic to cells, contributing to neuronal death.

Neuroinflammation: Chronic inflammation within the brain, particularly in the substantia nigra, plays a significant role in the progression of PD. Microglia, the brain's immune cells, become activated and may contribute to neuronal damage through the release of inflammatory mediators.

Oxidative Stress: Increased oxidative stress is evident in the PD brain, resulting from an imbalance between the generation of reactive oxygen species (ROS) and the brain's ability to detoxify these reactive intermediates. This stress further damages dopaminergic neurons.

Genetic Factors: Although most PD cases are sporadic, genetic predispositions have been identified. Mutations in genes such as LRRK2, PARK7, PINK1, and SNCA (which encodes alpha-synuclein) are associated with familial forms of PD.

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