Indicate the first gene to be identified as a cause of autosomal dominant Parkinsons’ Disease. How is this gene responsible for the characteristic morphological findings of the disease? What do you understand by the Triad of Parkinson’s Disease?
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SNCA was the first gene with mutations reported to cause autosomal-dominant PD.
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The SNCA gene provides instructions for making a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein is found mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. The release of neurotransmitters relays signals between neurons and is critical for normal brain function.
Although the function of alpha-synuclein is not well understood, studies suggest that it plays an important role in maintaining an adequate supply of synaptic vesicles in presynaptic terminals. It may also help regulate the release of dopamine, a neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements. Alpha-synuclein may also play a role in the movement of structures called microtubules that help cells maintain their shape.
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The clinical features historically associated with PD are the triad of motor symptoms, namely, tremor, rigidity, and bradykinesia, with postural instability often appearing as the disease progresses.
Symptoms: Constipation; Tremor; Dementia...
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