Seperate Roles In Alzheimer's Disease
1. Acetylcholine (ChA)
Acetylcholine (ChA) is a classical neurotransmitter, which is mainly located in neuromuscular junctions, where this chemical stimulates motor neurons to active muscles, in synapses and other sites across the central nervous system. Cholinergic neurons are the cells that uses acetylcholine to send its messages and perform other important functions [22].
Acetylcholine is synthesized in neuronal terminals from acetyl CoA and choline, the enzymes of this reaction is choline acetyltransferase (ChAT). The concentration of choline in plasma is about 10mM, from here it is taken up by cholinergic neurons through Na+/Choline transporter [Fig.6.] [22]. ChAT is an enzyme that synthesizes ChA and stores it in vesicles until the …show more content…
release into synaptic cleft by exocytosis, where it is degraded into choline by AChE or BuChE [23].
Acetycholine express its effect in the way as every biologically active substance does, by binding to the receptors on the cell’s surface. There are two main types of receptors on which ChA binds, it is nicotinic and muscarinic receptors. They mainly differ in their mechanism of signaling and outcomes. As the recent studies suggest, ChA plays an important role in suppressing the inflammatory response of lymphocytes, mediated by binding to a nicotinic receptor (a7-nAChRs) [24].
Cholinergic neurons are producing ChAT for their own functions, but as recent studies state, astrocytes are also producing this enzyme under active and resting conditions, it is well established that astrocytes can be cholinergic cells itself, since they express nicotinic receptors [22]. It was discovered that TNF - is one of the molecules that activate the astrocytes. As a result, high levels of choline acetyltransferase are found in CSF and extracellular fluid.
2.
Astrocyte roles in Alzheimer’s Disease (AD)
Alzheimer is a neurodegenerative diseases caused by the formation of amyloid- plaques, where A peptides clumpse together, that interupt the normal functioning of neurons. This results in loss of memory, changes in thinking and behaviour. The symptoms of alzheimer’s disease develop over the time [25]. A is a peptided formed from 42 different amino acids produced by amyloid precursor protein (APP).
It is well known that astrocytes have an impact on progression of Alzheimer’s disease. As some studies suggest, reactive astrocytes surround the formed plaques and undergo astrogliosis, where active astrocytes store large amounts of A, when in other brain tissues astroglial cells endure gradual loss of effectivness, which results in changes of synaptic plasticity and deterioration specific to Alzheimer [26]. Astrocytes are the cells, which degrade the amyloid- plaques and this happens during the astrocytic hypertorphic processes, therefore the deposit formation of the A in extracellular fluid is inhibited. Yet, it is not fully understood, how astrocytes manage to indetify and degrade amyloid-, but it is suggested that apolipo-protein E (ApoE), which is secreted by astrocytes, is responsible for this cellular process [27]. Besides that, asotryctes perform protective functions by suppressing activated microglia in
AD.
However, astrocytes not only have positive role in AD, but also make a negative impact. Failure of amyloid- plaques degradation by astrcoytes, results in formation of astrocytic plaques and accumulation of A in astrocytes. What is more, activated astrocytes, by stored amyloid-, produce inflammatory mediators as interleukin 1b (IL-1b) or tumor necrosis factor (TNF-), which cause neuronal injury. TNF- triggered by A increase calcium dependent glutamate production, which may result in neuronal death in Alzheimer’s disease. Glucose metabolism in astrocytes is also disturbed by A, resulting in damaged neuronal viability [27].
Acetylcholine (ChA) is a classical neurotransmitter, which is mainly located in neuromuscular junctions, where this chemical stimulates motor neurons to active muscles, in synapses and other sites across the central nervous system. Cholinergic neurons are the cells that uses acetylcholine to send its messages and perform other important functions [22].
Acetylcholine is synthesized in neuronal terminals from acetyl CoA and choline, the enzymes of this reaction is choline acetyltransferase (ChAT). The concentration of choline in plasma is about 10mM, from here it is taken up by cholinergic neurons through Na+/Choline transporter [Fig.6.] [22]. ChAT is an enzyme that synthesizes ChA and stores it in vesicles until the …show more content…
release into synaptic cleft by exocytosis, where it is degraded into choline by AChE or BuChE [23].
Acetycholine express its effect in the way as every biologically active substance does, by binding to the receptors on the cell’s surface. There are two main types of receptors on which ChA binds, it is nicotinic and muscarinic receptors. They mainly differ in their mechanism of signaling and outcomes. As the recent studies suggest, ChA plays an important role in suppressing the inflammatory response of lymphocytes, mediated by binding to a nicotinic receptor (a7-nAChRs) [24].
Cholinergic neurons are producing ChAT for their own functions, but as recent studies state, astrocytes are also producing this enzyme under active and resting conditions, it is well established that astrocytes can be cholinergic cells itself, since they express nicotinic receptors [22]. It was discovered that TNF - is one of the molecules that activate the astrocytes. As a result, high levels of choline acetyltransferase are found in CSF and extracellular fluid.
2.
Astrocyte roles in Alzheimer’s Disease (AD)
Alzheimer is a neurodegenerative diseases caused by the formation of amyloid- plaques, where A peptides clumpse together, that interupt the normal functioning of neurons. This results in loss of memory, changes in thinking and behaviour. The symptoms of alzheimer’s disease develop over the time [25]. A is a peptided formed from 42 different amino acids produced by amyloid precursor protein (APP).
It is well known that astrocytes have an impact on progression of Alzheimer’s disease. As some studies suggest, reactive astrocytes surround the formed plaques and undergo astrogliosis, where active astrocytes store large amounts of A, when in other brain tissues astroglial cells endure gradual loss of effectivness, which results in changes of synaptic plasticity and deterioration specific to Alzheimer [26]. Astrocytes are the cells, which degrade the amyloid- plaques and this happens during the astrocytic hypertorphic processes, therefore the deposit formation of the A in extracellular fluid is inhibited. Yet, it is not fully understood, how astrocytes manage to indetify and degrade amyloid-, but it is suggested that apolipo-protein E (ApoE), which is secreted by astrocytes, is responsible for this cellular process [27]. Besides that, asotryctes perform protective functions by suppressing activated microglia in
AD.
However, astrocytes not only have positive role in AD, but also make a negative impact. Failure of amyloid- plaques degradation by astrcoytes, results in formation of astrocytic plaques and accumulation of A in astrocytes. What is more, activated astrocytes, by stored amyloid-, produce inflammatory mediators as interleukin 1b (IL-1b) or tumor necrosis factor (TNF-), which cause neuronal injury. TNF- triggered by A increase calcium dependent glutamate production, which may result in neuronal death in Alzheimer’s disease. Glucose metabolism in astrocytes is also disturbed by A, resulting in damaged neuronal viability [27].