N-acetylaspartate
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N-acetylaspartate
''N''-Acetylaspartic acid, or ''N''-acetylaspartate (NAA), is a derivative of aspartic acid with a formula of C6H9NO5 and a molecular weight of 175.139. NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons, oligodendrocytes and myelin and is synthesized in the Mitochondrion, mitochondria from the amino acid aspartic acid and Acetyl-CoA, acetyl-coenzyme A. Function The various functions served by NAA are under investigation, but the primary proposed functions include: * Neuronal osmolyte that is involved in fluid balance in the brain * Source of acetate for lipid and myelin synthesis in oligodendrocytes, the Neuroglia, glial cells that myelinate neuronal axons * Precursor for the synthesis of the neuronal dipeptide N-Acetylaspartylglutamate * Contributor to energy production from the amino acid glutamate in neuronal mitochondria In the brain, NAA was thought to be present predominantly in neur ...
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Aspartoacylase
Aspartoacylase is a hydrolase, hydrolytic enzyme (, also called ''aminoacylase II'', ''ASPA'' and other names) that in humans is encoded by the ''ASPA'' gene. ASPA catalysis, catalyzes the deacylation of N-Acetylaspartate, ''N''-acetyl-l-aspartate (''N-acetylaspartate)'' into Aspartic acid, aspartate and acetate. It is a zinc-dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc-dependent hydrolases. It is most commonly found in the brain, where it controls the levels of ''N''-acetyl-l-aspartate. Mutations that result in loss of aspartoacylase activity are associated with Canavan disease, a rare dominance (genetics), autosomal recessive Neurodegeneration, neurodegenerative disease. Structure Aspartoacylase is a Dimer (chemistry), dimer of two identical monomers of 313 amino acids and uses a zinc cofactor in each. There are two distinct domains in each monomer: the N-terminal domain from residues 1-212 a ...
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Canavan Disease
Canavan disease, or Canavan-Van Bogaert-Bertrand disease, is a rare and fatal autosomal recessive degenerative disease that causes progressive damage to nerve cells and loss of white matter in the brain. It is one of the most common degenerative cerebral diseases of infancy. It is caused by a deficiency of the enzyme aminoacylase 2, and is one of a group of genetic diseases referred to as leukodystrophies. It is characterized by degeneration of myelin in the phospholipid layer insulating the axon of a neuron and is associated with a gene located on human chromosome 17. Symptoms and signs Symptoms of the most common (and most serious) form of Canavan disease typically appear in early infancy usually between the first three to six months of age. Canavan disease then progresses rapidly from that stage, with typical cases involving intellectual disability, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (i.e., initial floppiness - hypotonia - that ...
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In Vivo Magnetic Resonance Spectroscopy
In vivo magnetic resonance spectroscopy (MRS) is a specialized technique associated with magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS), also known as nuclear magnetic resonance (NMR) spectroscopy, is a non-invasive, ionizing-radiation-free analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders, Alzheimer's disease, depression, and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as muscles. In the case of muscles, NMR is used to measure the intramyocellular lipids content (IMCL). Magnetic resonance spectroscopy is an analytical technique that can be used to complement the more common magnetic resonance imaging (MRI) in the characterization of tissue. Both techniques typically acquire signal from hydrogen protons (other endogenous nuclei such as those of Carbon, Nitrogen, and Phosphorus are also used), but MRI acquires signal primarily from prot ...
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N-Acetylaspartylglutamate
''N''-Acetylaspartylglutamic acid (''N''-acetylaspartylglutamate or NAAG) is a peptide neurotransmitter and the third-most-prevalent neurotransmitter in the mammalian nervous system. NAAG consists of ''N''-acetylaspartic acid (NAA) and glutamic acid coupled via a peptide bond. NAAG was discovered as a nervous system-specific peptide in 1965 by Curatolo and colleagues but initially disregarded as a neurotransmitter and not extensively studied. However it meets the criteria for a neurotransmitter, including being concentrated in neurons, packed in synaptic vesicles, released in a calcium-dependent manner, and hydrolyzed in the synaptic space by enzymatic activity. NAAG activates a specific receptor, the metabotropic glutamate receptor type 3. It is synthesized enzymatically from its two precursors and catabolized by NAAG peptidases in the synapse. The inhibition of the latter enzymes has potentially important therapeutic effects in animal models of several neurologic conditio ...
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Acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production. Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid (B5) through an amide linkage and 3'-phosphorylated ADP. The acetyl group (indicated in blue in the structural diagram on the right) of acetyl-CoA is linked to the sulfhydryl substituent of the β-mercaptoethylamine group. This thioester linkage is a "high energy" bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol). CoA is acetylated to acetyl-CoA by the breakdown of carbohydrates through glycolysis and by the breakdown of fatty acids through β-oxidation. Acetyl-CoA then enters the citric acid cycle, where the acetyl group is oxidized to carbon dioxide and ...
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Metabotropic Glutamate Receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter. Function and structure The mGluRs perform a variety of functions in the central and peripheral nervous systems: For example, they are involved in learning, memory, anxiety, and the perception of pain. They are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum, and the cerebral cortex, as well as other parts of the brain and in peripheral tissues. Like other metabotropic receptors, mGluRs have seven transmembrane domains that span the cell membrane. Unlike ionotropic receptors, metabotropic glutamate receptors are not ion channels. Instead, they activate biochemical cascades, leading to the modification of o ...
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Neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are released from synaptic vesicles into the synaptic cleft where they are able to interact with neurotransmitter receptors on the target cell. The neurotransmitter's effect on the target cell is determined by the receptor it binds. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available and often require a small number of biosynthetic steps for conversion. Neurotransmitters are essential to the function of complex neural systems. The exact number of unique neurotransmitters in humans is unknown, but more than 100 have been identified. Common neurotransmitters include glutamate, GABA, acetylcholine, glycine and norepinephrine. Mechanism and cycle Synthes ...
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Working Memory
Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, but some theorists consider the two forms of memory distinct, assuming that working memory allows for the manipulation of stored information, whereas short-term memory only refers to the short-term storage of information. Working memory is a theoretical concept central to cognitive psychology, neuropsychology, and neuroscience. History The term "working memory" was coined by Miller, Galanter, and Pribram, and was used in the 1960s in the context of theories that likened the mind to a computer. In 1968, Atkinson and Shiffrin used the term to describe their "short-term store". What we now call working memory was formerly referred to variously as a "short-term store" or short-term memory, primary memory, immediate memory, operant memo ...
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Hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper (also called ''Ammon's horn''), and the dentate gyrus. In Alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result from ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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Stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, dizziness, or loss of vision to one side. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours, the stroke is a transient ischemic attack (TIA), also called a mini-stroke. A hemorrhagic stroke may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia and loss of bladder control. The main risk factor for stroke is high blood pressure. Other risk factors include high blood cholesterol, tobacco smoking, obesity, diabetes mellitus, a previous TIA, end-st ...
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Neuroglia
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia, and in the peripheral nervous system they include Schwann cells and satellite cells. Function They have four main functions: *to surround neurons and hold them in place *to supply nutrients and oxygen to neurons *to insulate one neuron from another *to destroy pathogens and remove dead neurons. They also play a role in neurotransmission and synaptic connections, and in physiological processes such as breathing. While glia were thought to outnumber neurons by a ratio of 10:1, recent studies using newer methods and reappraisal of historical qua ...
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