- Parkinson's Disease was first described in “Essay on the Shaking Palsy”, by Dr. James Parkinson in 1817.
- Progressive disorder of the central nervous system
- Affects several regions of the brain, including an area called the substantia nigra in the midbrain that controls balance and movement.
- May also affect regions of the brain that regulate involuntary functions such as blood pressure and heart activity.
- Symptoms of Parkinsonism includes the head held forward, drooping eyelids (ptosis), open mouth, and salivary drooling, tremor of hands, and slow, shuffling gait, and short steps.
- Acronym for Parkinsonism symptoms is TRAP (Tremors, Rigidity, Akinesia, and Postural Instability)
- Tremors are involuntary trembling of the limbs
- Rigidity is stiffness of the muscles
- Akinesia is lack of movement of slowness in initiating and maintaining movement
- Postural Instability is characteristic bending or flexion of the body associated with difficulty in balance and disturbances in gait.
- Symptoms are due to a drastic drop in brain dopamine levels in the substantia nigra.
- Dopamine is responsible for the smooth functioning of the basal ganglia in the mid-brain
- Reduction of dopamine is primarily due to >90% loss of dopaminergic neurons in the substantia nigra region of the mid-brain
- Presence of characteristic Lewy Body formation in substantia nigra.
- α-synuclein is abundant in nerve cells in the brain, and smaller amounts are found in the heart, muscles, and other tissues.
- In the brain, α-synuclein localizes mainly at the tips of nerve cells in specialized structures called presynaptic terminals.
- In these structures, α-synuclein interacts with fats (lipids) and other proteins.
- There are three possible mutations that cause misfolding of α-synuclein. Ala53Thr, Ala30Pro, and Glu46Lys.
- Parkinson's Disease results from the loss of neurons in the substantia nigra and dopamine levels in the corpus striatum.
- This disease is characterized by tremors and muscle weakness that usually develop late in lif.e
- Parkinson's Disease may exhibit autosomal dominant inheritance.
- Neurodegenerative disease, characterized clinically by parkinsonism, defined by resting tremor, slow voluntary movements (hypokinetic disorders), and movements with rigidity.
- Parkinson's Disease is pathologically defined by a loss of dopaminergic neurons from the substantia nigra and proteinaceous deposits in the cytoplasm of neurons (Lewy bodies) and threadlike inclusions in axons (Lewy neurites).
- The protein α-synuclein is present in Lewy Bodies and axons.
- Classical Lewy bodies are associated with nerve cell death in one specific nucleus of the brain (substantia nigra) in nearly all cases of Parkinson's Disease.
- In parkinsonism, there is no problem with the spinal cord or something else, there is an issue with the brain, and this causes spasticity.
- Lesions of the substantia nigra are caused by destruction of dopaminergic neurons
- Occur in patients with Parkinson's disease.
- Since dopamine inhibits the indirect (inhibitory) pathway and excites the direct (excitatory) pathway, destruction of dopaminergic neurons is, overall, inhibitory.
- Symptoms include lead-pipe rigidity, tremor, and reduced voluntary movement.
- Involves degeneration of dopaminergic neurons that use the D2 receptors.
- D2 receptors inhibit adenylate cyclase via a Gi protein.
- Dopaminergic endings are particularly numerous in the corpus striatum, limkbic system and cerebral cortex. Pathological reduction in dopaminergic activity has widespread effects on motor control, affective behaviour and other neural activities, as seen in Parkinson's Syndrome.
- In Parkinson's Disease, microglia become phagocytic.
- In Parkinson's Disease, there is decreased output in the substantia nigra pars compacta, globus pallidus, ventral anterior nucleus, and the cortex.
- Dopamine is the neurotransmitter that decreases in Parkinson's disease.
- Lesions of the substantia nigra are caused by destruction of dopaminergic neurons
- Occur in patients with Parkinson's disease.
- Since dopamine inhibits the indirect (inhibitory) pathway and excites the direct (excitatory) pathway, destruction of dopaminergic neurons is, overall, inhibitory.
- Symptoms include lead-pipe rigidity, tremor, and reduced voluntary movement.
- Involves degeneration of dopaminergic neurons that use the D2 receptors.
- D2 receptors inhibit adenylate cyclase via a Gi protein.
- Dopaminergic endings are particularly numerous in the corpus striatum, limkbic system and cerebral cortex. Pathological reduction in dopaminergic activity has widespread effects on motor control, affective behaviour and other neural activities, as seen in Parkinson's Syndrome.
- In Parkinson's Disease, microglia become phagocytic.
- In Parkinson's Disease, there is decreased output in the substantia nigra pars compacta, globus pallidus, ventral anterior nucleus, and the cortex.
- Dopamine is the neurotransmitter that decreases in Parkinson's disease.
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