Huntingtin: Difference between revisions

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==Huntingtin Protein==

Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease''' (HD). The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Huntington disease is a bit unusual, regarding the fact that there may be a progressive increase in the severity of a mutation, and sometimes in the probability that a given mutation will result in a disease, as it is passed from parents to their offspring. This may be caused due to polymerase slippage in this case. Probably the most prominent hallmark of HD is the formation of inclusion bodies. Mutant huntingtin (mHTT) is prone to conformational changing that can lead to the formation of very stable anti-parallel β-sheets; more specifically, amyloid structures <ref>DOI 10.1016/s0306-4522(00)00391-2</ref>. ~~Yet, despite~~ its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>.

Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease''' (HD). The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Huntington disease is a bit unusual, regarding the fact that there may be a progressive increase in the severity of a mutation, and sometimes in the probability that a given mutation will result in a disease, as it is passed from parents to their offspring. This may be caused due to polymerase slippage in this case. Probably the most prominent hallmark of HD is the formation of inclusion bodies. Mutant huntingtin (mHTT) is prone to conformational changing that can lead to the formation of very stable anti-parallel β-sheets; more specifically, amyloid structures <ref>DOI 10.1016/s0306-4522(00)00391-2</ref>. Despite its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>.

Huntingtin: Difference between revisions

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 ==Huntingtin Protein==
 <StructureSection load='6EZ8' size='340' side='right' caption='Human Huntingtin-HAP40 complex structure obtained by cryo-electron microscopy; blue - huntingtin protein, green - HAP40' scene=''>
-Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease''' (HD). The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Huntington disease is a bit unusual, regarding the fact that there may be a progressive increase in the severity of a mutation, and sometimes in the probability that a given mutation will result in a disease, as it is passed from parents to their offspring. This may be caused due to polymerase slippage in this case. Probably the most prominent hallmark of HD is the formation of inclusion bodies. Mutant huntingtin (mHTT) is prone to conformational changing that can lead to the formation of very stable anti-parallel β-sheets;   more   specifically,   amyloid structures <ref>DOI 10.1016/s0306-4522(00)00391-2</ref>. Yet, despite its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>.
+Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease''' (HD). The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Huntington disease is a bit unusual, regarding the fact that there may be a progressive increase in the severity of a mutation, and sometimes in the probability that a given mutation will result in a disease, as it is passed from parents to their offspring. This may be caused due to polymerase slippage in this case. Probably the most prominent hallmark of HD is the formation of inclusion bodies. Mutant huntingtin (mHTT) is prone to conformational changing that can lead to the formation of very stable anti-parallel β-sheets;   more   specifically,   amyloid structures <ref>DOI 10.1016/s0306-4522(00)00391-2</ref>. Despite its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>.