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Parkinson's Cell Signaling Communication

Learning what truly goes on inside the body when someone has Parkinson's Disease!
by

Liann Little

on 13 December 2012

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Transcript of Parkinson's Cell Signaling Communication

Parkinson's Disease Cell Signaling Pathways Involved The Normal Way: What is the Signaling Mechanism? Dopamine: Basics of Signal Transduction Pathway Current Research! What is Parkinson's Disease?
Parkinson's disease is a disorder of the brain that leads to shaking (tremors) and difficulty with walking, movement and coordination.
Here are some famous people we know with Parkinson's Disease!
Michael J. Fox Muhammad Ali What are the symptoms? Symptoms may be mild at first, and may affect one or both sides of the body. They can include:
- Slow blinking
- Constipation
- Difficulty swallowing
Shaking:
Occurs in the limbs at rest, or when the arm and leg is held out.
It goes away when you move
May be seen in the head, lips, tongue and feet
-The release of the neurotransmitter dopamine in the presynaptic neuron result in signaling in the postsynaptic neuron through D1 and D2 type dopamine receptors.
- D1 receptors signal through G-proteins to activate adenylate cyclase, causing cAMP formation and activation of PKA. D2 type receptors block signaling by inhibiting adenylate cyclase. The Parkinson's Way: -Mitochondria are the cell's "power plants," which metabolize oxygen and generate energy. Oxidative stress is the damage caused to cells by reactive oxygen produced during oxygen metabolism.
- The Mitochondria protein PINK1 protects the cell from oxidative stress and promotes cell survival by regulating the protein TRAP1. When PINK1 is mutated the protective TRAP1 is damaged, leading to Mitochondria damage.
-When this happens, there is an over abundance of a-synuclein, which become Lewy Bodies, abnormal aggregates of proteins that block the creation of Dopamine.
-In the end, the receptors never get the call for control the motor skills, resulting in the excess physical movement. Key note: Presynaptic neuron terminals are the ones that release a neurotransmitter in response to an action potential. A prosynaptic neuron recieves the electrical impulse that is transmitted from the synaptic cleft! Dopamine is a chemical created by the nerve cells. It sends signals to the part of the brain that controls movement.
When the nerve cells break down, they cannot create dopamine. The Type of Receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors. The signal transduction pathway for dopamine in Parkinson's disease is exactly the same as in normal brain, the only difference is that there are not too many dopamine neurons left in Parkinson's brains. But the receptor, which is coupled to the G-protein, and then to adenylyl cyclase, is exactly the same. Cellular/Organism response to Parkinson's Disease The cellular responses to Parkinson's are apoptosis, which is the process of programmed cell death. A few examples could be: cell shrinkage, chromatin condensation, and blebbing; an irregular bulge in the plasma membrane. Faulty Mechanism Faulty Mechanisms include the idea of losing brain cells. There are many ways that this could happen:
1. One mechanism consist of an abnormal accumulation of the protein a-synuclein that binds to ubiquitin, a protein that directs all other proteins to their comparements, in the damaged cell.
2. Another faulty mechanism could be the lack of mitochondrial activity. Correct Mechanism The correct mechanism would be the right amount of dopamine traveling through the receptors to control excess motor movement. Currently there is no cure for Parkinson's Disease. There are treatments available to lessen the effects of Parkinson’s symptoms for some window of time, but this is all they can do. What they haven't discovered is a disease-modifying treatment, something that would actually halt or slow the progression of the disease. There are have dopamine replacement therapies, like Levodopa. In the 1970s, Levodopa was the first drug approved specifically for Parkinson's disease. Levodopa is converted by enzymes in the brain to produce dopamine, replacing the ones lost. It improved mobility and allowed people to function normally in the early stages of the disease. Although the symptoms started to come back before it was time for another dose of the drug. Michael J. Fox's Foundation works toward a goal to find a cure for Parkinson's, one that can someday take away the disease as a whole, not just cover up symptoms. The funded research has raised over hundreds of millions of dollars to try and find this cure and make it affordable for all people.
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