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In excitotoxicity,nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high,resulting in excessive stimulation of receptors. For example,when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter,glutamate,significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes,including phospholipases,endonucleases,and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton,membrane,and DNA. In evolved,complex adaptive systems such as biological life it must be understood that mechanisms are rarely,if ever,simplistically direct. For example,NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate.
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Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate –the principal excitatory neurotransmitter –across a membrane. The family of glutamate transporters is composed of two primary subclasses:the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. In the brain,EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons,while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues,including the heart,liver,testes,and bone. They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate.
Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases. PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex,spinal cord,brain stem,and pyramidal tracts. This specifically involves the glossopharyngeal nerve (IX),vagus nerve (X),and hypoglossal nerve (XII).
Excitatory amino acid transporter 1 (EAAT1) is a protein that,in humans,is encoded by the SLC1A3 gene. EAAT1 is also often called the GLutamate ASpartate Transporter 1 (GLAST-1).
Natural resistance-associated macrophage protein 2,also known as divalent metal transporter 1 (DMT1) and divalent cation transporter 1 (DCT1),is a protein that in humans is encoded by the SLC11A2 gene. DMT1 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans.
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Excitatory amino acid transporter 2 (EAAT2) also known as solute carrier family 1 member 2 (SLC1A2) and glutamate transporter 1 (GLT-1) is a protein that in humans is encoded by the SLC1A2 gene. Alternatively spliced transcript variants of this gene have been described,but their full-length nature is not known.
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Excitatory amino acid transporter 3 (EAAT3),is a protein that in humans is encoded by the SLC1A1 gene.
Neutral amino acid transporter B(0) is a protein that in humans is encoded by the SLC1A5 gene.
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There are more than 25 genes known to be associated with amyotrophic lateral sclerosis (ALS) as of June 2018,which collectively account for about 70% of cases of familial ALS (fALS) and 10% of cases of sporadic ALS (sALS). About 5–10% of cases of ALS are directly inherited. Overall,first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance,meaning that mutations in two or more genes are required to cause disease.
Tom Otis is an American researcher,academic and author. He is the Chief Scientific Officer at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour and holds a Professorship in Neuroscience at University College London.
Georg Bernhard Landwehrmeyer FRCP is a German neurologist and neuroscientist in the field of neurodegeneration primarily focusing on Huntington's disease. Landwehrmeyer is a professor of neurology at Ulm University Hospital. He was one of the founders of the European Huntington's Disease Network (EHDN) in 2004 and was chairman of its executive committee until 2014.
References
- ↑ "Ralph W. Kuncl will be new president of University of Redlands". Los Angeles Times. June 3, 2012. Retrieved 2 March 2017.
- ↑ "University of Rochester Provost Ralph W. Kuncl named President of University of Redlands". University of Rochester. Retrieved 2021-08-03.
- ↑ Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski M, and Peper, MJ: Colchicine myopathy and neuropathy. N Engl J Med 316:1562-1568, 1987. (Selected for review and editorial in Lancet and British Medical Journal).
- ↑ Rothstein JD, Tsai G, Kuncl RW, Clawson LL, Cornblath DR, Drachman DB, Pestronk A, Stauch BL, Coyle JT: Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 28:18-25, 1990.
- ↑ Rothstein JD, Martin LJ, Kuncl RW: Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464-68, 1992. (Top 5 papers, ISI Citation Index, March-April 1994).
- ↑ Rothstein JD, VanKammen M, Levey AI, Martin L, Kuncl RW: Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:73-84, 1995.
- ↑ Rothstein JR, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke J, Welty DF: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675-686, 1996.
- ↑ "Official Presidential Biography" (PDF). University of Redlands. Retrieved 3 August 2021.
- ↑ https://annapolissymphony.org/news/ceo/