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Muscarinic Cholinergic Receptors: by Monali Desai (with additions by Don DeWitt, PhD) for Molecular Biology 5, 2005-2006 (version 1.0) |
| Return
to Student Lessons |
| . Table of Contents |
|
| 1. | GENERAL
INFORMATION |
| 2. | LOCATION & FUNCTION |
| 3. | STRUCTURE |
| 4. | SIGNAL
TRANSDUCTION Introduction G-Protein Coupling Second-Messengers in M2 Receptors in M3 Receptors |
| 5. | ALZHEIMER'S
DISEASE |
| 6. | SOURCES |
What is
it?
Alzheimer’s is a progressive brain disorder where there is a loss of cholinergic neurons in the brain because of the buildup of amyloid plaques and neurofibrillary tangles. The degeneration of these neurons results in extreme loss of memory, ability to learn, judgment, and communication. As the disease progresses, the brain shrinks. At first, cells in the hippocampus disintegrate and short-term memory suffers. The sufferer is unable to perform routine tasks. In the next few stages of the disease, the cerebral cortex is affected and thus, language, emotion, and language is impaired. In the later stages, more nerve cell death may lead to behavioral changes such as wandering and agitation. In the last stages, the ability to recognize faces and communication is completely lost, along with bowel and bladder control. The patients obviously would need constant care until, at last, the patient will die within a few years.
How Can it be Treated?
Although the effects of the disease are irreversible, by diagnosing and treating the disease early on, the quality of life for the individuals can improve. Muscarinic receptors M1 and M5 are excitatory and found in the cortex and hippocampus (where cholinergic neurons are being lost). Thus, these sites are targets for Alzheimer’s drugs. Drug companies want to develop muscarinic receptor agonists that replace acetylcholine, which is depleted as the neurons degenerate. The ideal drug would have a high efficacy and selectivity for forebrain receptors and minimal adverse effects. A few cholinergic agonists on the market now are RS86, Bethanecol, Arecoline, and Oxotremorine.
But as mentioned before, amyloid plaques are The hallmark of Alzheimer’s disease, and so much effort and focus is being placed on eradicating these buildups than on cholinergic agonists.
Figure 11. As the figure says, this is one method of treatment for Alzheimer’s
disease aggressively pursued by researchers (modified from ref).
Alzheimer’s is a progressive brain disorder where there is a loss of cholinergic neurons in the brain because of the buildup of amyloid plaques and neurofibrillary tangles. The degeneration of these neurons results in extreme loss of memory, ability to learn, judgment, and communication. As the disease progresses, the brain shrinks. At first, cells in the hippocampus disintegrate and short-term memory suffers. The sufferer is unable to perform routine tasks. In the next few stages of the disease, the cerebral cortex is affected and thus, language, emotion, and language is impaired. In the later stages, more nerve cell death may lead to behavioral changes such as wandering and agitation. In the last stages, the ability to recognize faces and communication is completely lost, along with bowel and bladder control. The patients obviously would need constant care until, at last, the patient will die within a few years.
How Can it be Treated?
Although the effects of the disease are irreversible, by diagnosing and treating the disease early on, the quality of life for the individuals can improve. Muscarinic receptors M1 and M5 are excitatory and found in the cortex and hippocampus (where cholinergic neurons are being lost). Thus, these sites are targets for Alzheimer’s drugs. Drug companies want to develop muscarinic receptor agonists that replace acetylcholine, which is depleted as the neurons degenerate. The ideal drug would have a high efficacy and selectivity for forebrain receptors and minimal adverse effects. A few cholinergic agonists on the market now are RS86, Bethanecol, Arecoline, and Oxotremorine.
But as mentioned before, amyloid plaques are The hallmark of Alzheimer’s disease, and so much effort and focus is being placed on eradicating these buildups than on cholinergic agonists.
Figure 11. As the figure says, this is one method of treatment for Alzheimer’s
disease aggressively pursued by researchers (modified from ref).
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