Alzheimer’s is a common neurodegenerative disease that accounts for the majority of all cases of dementia (Advokat, Comaty & Julien, 2014). Although the exact cause of Alzheimer’s is unknown, it is hypothesized that two systems crucial for the communication between brain cells fail due to the down regulation of acetylcholine and the over activation of glutamate, which result in the death of neurons (IOS Press, 2008). It is believed to involve the irreversible loss of cholinergic neurons, specifically in the cerebral cortex and hippocampus (Advokat et al., 2014). The onset of this disease usually occurs after age 60, but is increasingly being reported in people younger than 65 (Advokat et al., 2014). Symptoms of Alzheimer’s involve cognitive
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The definitive diagnosis of Alzheimer’s can’t be made until autopsy, when neuronal loss, accumulation of beta-amyloid plaques, neurofibrillary tangles and abnormal tau microtubules are observed (Advokat et al., 2014). The current drugs that treat Alzheimer’s act on brain neurotransmitters, but do not alter the course of the disease (Advokat et al., 2014). Some of the drugs for the treatment of Alzheimer’s disease focus on inhibiting the enzyme that breaks down acetylcholine in the synapse called acetyl cholinesterase inhibitors (Advokat et al., 2014). Donepezil, galantamine, and rivastigmine are examples of acetyl cholinesterase inhibitors (AChE-Is) that are currently prescribed to patients suffering from Alzheimer’s disease (Hansen et al., 2008). Side effects associated with these AChE-Is include nausea, diarrhea, abdominal cramping and anorexia (Advokat et al., 2014). These drugs are problematic because they are usually only associated with a very small improvement in cognitive improvement from baseline. These improvements do not remain constant and patients’ cognitive symptoms get increasingly worse as the disease …show more content…
Acetylcholine is a neurotransmitter, which plays a role in synaptic plasticity, learning and memory. It has been observed that there is approximately a 90% loss of acetylcholine in the brains of people afflicted with Alzheimer’s disease (Boeree, 2009). The α-7 nicotinic acetylcholine receptors (α7- nAChRs) are highly expressed in the hippocampus (Prickaerts et al., 2011). Hippocampal long-term potentiation (LTP) is the constant increase in the efficiency of synaptic transmission. Research supports the hypothesis that α-7 nAChR agonists improve LTP and the formation of long-term memory in animal models due to the activation of the MAPK signaling pathway, with phosphorylation of ERK and CREB. α-7 nAChR agonists also improved learning and memory task performance in mice. With the intention of reducing cognitive impairments and improving memory in those afflicted with Alzheimer’s disease, Marquadraezon will be a partial agonist at the α-7 nACh receptor. This receptor has two pockets in which the drug may bind. Thus, to activate the receptor two molecules must bind. The receptor will be exposed to a low concentration of the high affinity drug and when exposed to both the drug and low affinity acetylcholine, the receptor will be quickly activated (Prickaerts et al., 2011). Thus, the binding of the Marquadraezon with the co-agonist
The definitive diagnosis of Alzheimer’s can’t be made until autopsy, when neuronal loss, accumulation of beta-amyloid plaques, neurofibrillary tangles and abnormal tau microtubules are observed (Advokat et al., 2014). The current drugs that treat Alzheimer’s act on brain neurotransmitters, but do not alter the course of the disease (Advokat et al., 2014). Some of the drugs for the treatment of Alzheimer’s disease focus on inhibiting the enzyme that breaks down acetylcholine in the synapse called acetyl cholinesterase inhibitors (Advokat et al., 2014). Donepezil, galantamine, and rivastigmine are examples of acetyl cholinesterase inhibitors (AChE-Is) that are currently prescribed to patients suffering from Alzheimer’s disease (Hansen et al., 2008). Side effects associated with these AChE-Is include nausea, diarrhea, abdominal cramping and anorexia (Advokat et al., 2014). These drugs are problematic because they are usually only associated with a very small improvement in cognitive improvement from baseline. These improvements do not remain constant and patients’ cognitive symptoms get increasingly worse as the disease …show more content…
Acetylcholine is a neurotransmitter, which plays a role in synaptic plasticity, learning and memory. It has been observed that there is approximately a 90% loss of acetylcholine in the brains of people afflicted with Alzheimer’s disease (Boeree, 2009). The α-7 nicotinic acetylcholine receptors (α7- nAChRs) are highly expressed in the hippocampus (Prickaerts et al., 2011). Hippocampal long-term potentiation (LTP) is the constant increase in the efficiency of synaptic transmission. Research supports the hypothesis that α-7 nAChR agonists improve LTP and the formation of long-term memory in animal models due to the activation of the MAPK signaling pathway, with phosphorylation of ERK and CREB. α-7 nAChR agonists also improved learning and memory task performance in mice. With the intention of reducing cognitive impairments and improving memory in those afflicted with Alzheimer’s disease, Marquadraezon will be a partial agonist at the α-7 nACh receptor. This receptor has two pockets in which the drug may bind. Thus, to activate the receptor two molecules must bind. The receptor will be exposed to a low concentration of the high affinity drug and when exposed to both the drug and low affinity acetylcholine, the receptor will be quickly activated (Prickaerts et al., 2011). Thus, the binding of the Marquadraezon with the co-agonist