Protein blocks cell death in neurons
One million people in the U.S. alone currently suffer from a disease that James Parkinson, a British General Practitioner, first described in 1817 as "the Shaking Palsy." Later renamed for him, Parkinson's disease (PD) now presents itself as one of the most well-known, devastating and debilitating motor disorders.
The list of past and present sufferers includes several well known individuals, including Michael J. Fox, Muhammad Ali, Pope John Paul II, Janet Reno (former U.S. Attorney General), Mao Zedong, James Doohan (the original Scotty of Star Trek) and Johnny Cash.
Parkinson's is characterized by several identifying features. Most relate to decreased ease or control of movement, tremors (especially in the hands), postural instability, slowness of movement, stooped posture and rigidity of the trunk and/or limbs.
Not all sufferers experience all of these symptoms, and their severity fluctuates from person to person. Nevertheless, as the disease progresses, the symptoms generally get worse, often to the point of almost complete debilitation.
Parkinson's is not well understood, though scientists have concluded that PD results from the loss of dopaminergic neurons in the brain. These neurons are responsible for neuron-to-neuron signaling by way of the neurotransmitter dopamine. The cells that are lost in Parkinson's are those found in a brain region called the substantia nigra.
The substantia nigra is a region directly related to the motor system, so the loss of these dopaminergic neurons is highly detrimental to the motor system, and faithfully describes the motor impairments seen in PD.
The lack of understanding of the disease, as well as the support of several famous people who suffer from PD, has helped to propel Parkinson's research forward. Nevertheless, much remains a mystery, which is why discoveries like the one by W. W. Smith, X. Li and colleagues at the Hopkins School of Medicine, the University of Maryland School of Pharmacy and the Xi'an Jiaotong University School of Medicine in China are very exciting.
The team thinks that they have found at least one of the cellular, molecular bases for a possible protective effect against the selective death of dopaminergic substantia nigra cells in the brains of those who suffer from Parkinson's disease.
In particular, the researchers have seen that when a cytoplasmic protein, called synphilin-1, is present at high levels in neuron cells, it can help increase neuronal growth and development. Conversely, a lack of the protein has the opposite effect, with the added detriment of neural toxicity.
More importantly, in the presence of a toxin, synphilin-1 has been shown to provide a protective - and therefore potentially therapeutic - role. The toxin, a commonly used natural pesticide called Rotenone, is also an inhibitor of one of the enzymes in a key process in the creation of ATP, the molecular fuel that the cell uses for energy.
High Rotenone levels would be detrimental and even potentially deadly for a cell, which would be unable to produce enough energy to fulfill its basic metabolic duties. Previous studies have observed that high levels of Rotenone can lead to PD symptoms in both rats and in the fruit fly Drosophila.
However, synphilin-1 activity helps to reduce the damage caused by Rotenone. Synphilin-1 blocks the apoptotic (cell death) pathway initiated by Rotenone. Synphilin-1 prevents cell death by decreasing the level of two enzymes within the cell that are involved in apoptosis, caspase-3 and poly ADP-ribose polymerase (PARP).
In addition to protecting against damage caused by Rotenone, synphilin-1 can also activate a special class of proteins, called extracellular signal-regulated kinases (ERKs). These ERKs help to promote growth and differentiation of new neurons or can also protect against cellular damage.
Thus, the fact that synphilin-1 enhances ERK activities may suggest the mechanism by which synphilin-1 helps neurons to grow, differentiate and survive even in the face of stressors such as toxins.
Other previous studies have found that synphilin-1 can interact with proteins that then go on to destroy any malfunctioning proteins. This suggests that synphilin-1 might also prevent the negative consequences of having dangerous proteins around by aiding in the breakdown of those proteins.
Mutations of synphilin-1 have been seen in those with PD, and such mutations decrease cells' abilities to handle environmental stressors. These cells are damaged and potentially killed more easily when synphilin-1 is absent or present at decreased levels.
These findings converge on one important point: If synphilin-1 can do all of these things, the protein may be a good target for therapy and may provide protection against Parkinson's disease.
The list of past and present sufferers includes several well known individuals, including Michael J. Fox, Muhammad Ali, Pope John Paul II, Janet Reno (former U.S. Attorney General), Mao Zedong, James Doohan (the original Scotty of Star Trek) and Johnny Cash.
Parkinson's is characterized by several identifying features. Most relate to decreased ease or control of movement, tremors (especially in the hands), postural instability, slowness of movement, stooped posture and rigidity of the trunk and/or limbs.
Not all sufferers experience all of these symptoms, and their severity fluctuates from person to person. Nevertheless, as the disease progresses, the symptoms generally get worse, often to the point of almost complete debilitation.
Parkinson's is not well understood, though scientists have concluded that PD results from the loss of dopaminergic neurons in the brain. These neurons are responsible for neuron-to-neuron signaling by way of the neurotransmitter dopamine. The cells that are lost in Parkinson's are those found in a brain region called the substantia nigra.
The substantia nigra is a region directly related to the motor system, so the loss of these dopaminergic neurons is highly detrimental to the motor system, and faithfully describes the motor impairments seen in PD.
The lack of understanding of the disease, as well as the support of several famous people who suffer from PD, has helped to propel Parkinson's research forward. Nevertheless, much remains a mystery, which is why discoveries like the one by W. W. Smith, X. Li and colleagues at the Hopkins School of Medicine, the University of Maryland School of Pharmacy and the Xi'an Jiaotong University School of Medicine in China are very exciting.
The team thinks that they have found at least one of the cellular, molecular bases for a possible protective effect against the selective death of dopaminergic substantia nigra cells in the brains of those who suffer from Parkinson's disease.
In particular, the researchers have seen that when a cytoplasmic protein, called synphilin-1, is present at high levels in neuron cells, it can help increase neuronal growth and development. Conversely, a lack of the protein has the opposite effect, with the added detriment of neural toxicity.
More importantly, in the presence of a toxin, synphilin-1 has been shown to provide a protective - and therefore potentially therapeutic - role. The toxin, a commonly used natural pesticide called Rotenone, is also an inhibitor of one of the enzymes in a key process in the creation of ATP, the molecular fuel that the cell uses for energy.
High Rotenone levels would be detrimental and even potentially deadly for a cell, which would be unable to produce enough energy to fulfill its basic metabolic duties. Previous studies have observed that high levels of Rotenone can lead to PD symptoms in both rats and in the fruit fly Drosophila.
However, synphilin-1 activity helps to reduce the damage caused by Rotenone. Synphilin-1 blocks the apoptotic (cell death) pathway initiated by Rotenone. Synphilin-1 prevents cell death by decreasing the level of two enzymes within the cell that are involved in apoptosis, caspase-3 and poly ADP-ribose polymerase (PARP).
In addition to protecting against damage caused by Rotenone, synphilin-1 can also activate a special class of proteins, called extracellular signal-regulated kinases (ERKs). These ERKs help to promote growth and differentiation of new neurons or can also protect against cellular damage.
Thus, the fact that synphilin-1 enhances ERK activities may suggest the mechanism by which synphilin-1 helps neurons to grow, differentiate and survive even in the face of stressors such as toxins.
Other previous studies have found that synphilin-1 can interact with proteins that then go on to destroy any malfunctioning proteins. This suggests that synphilin-1 might also prevent the negative consequences of having dangerous proteins around by aiding in the breakdown of those proteins.
Mutations of synphilin-1 have been seen in those with PD, and such mutations decrease cells' abilities to handle environmental stressors. These cells are damaged and potentially killed more easily when synphilin-1 is absent or present at decreased levels.
These findings converge on one important point: If synphilin-1 can do all of these things, the protein may be a good target for therapy and may provide protection against Parkinson's disease.
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Monodb
Monodb
posted 11/13/09 @ 1:54 PM EST
This article is a model of responsible presentation of useful information which should be a standard for those purporting to pass on such knowledge. It seems to me that most articles with such purpose for PS are tragically shallow and only address the symptoms that make the ignorant public uncomfortable to observe. (Continued…)
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