2011 Group Project 4 - Revision history

Z8600021 at 00:54, 19 November 2019

2019-11-19T00:54:40Z

S8600021 at 02:11, 28 October 2011

2011-10-28T02:11:52Z

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	{{2011ProjectsMH}}		{{2011ProjectsMH}}




	~~----~~

	=Huntington's Disease=		=Huntington's Disease=

S8600021: Protected "2011 Group Project 4": Protect from student change ([edit=sysop] (indefinite) [move=sysop] (indefinite))

2011-10-13T06:22:05Z

Protected "2011 Group Project 4": Protect from student change ([edit=sysop] (indefinite) [move=sysop] (indefinite))

← Older revision	Revision as of 16:22, 13 October 2011
(No difference)

Z3290558: /* Clinical Manifestations */

2011-10-13T05:12:39Z

Clinical Manifestations

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	==Clinical Manifestations==		==Clinical Manifestations==

			[[Image:Peripheral and Central Nervous System impairment in Huntington's Disease..JPG\|thumb\|right\|Symptoms and impairment of the human body that manifests in patients diagnosed of Huntington's Disease regardless of gender\|500px]]

	As previously mentioned, Huntington’s Disease is a [[#Hyperkinetic disorder\|hyperkinetic disorder]] which is caused by the degeneration of neurons in the cerebral cortex and striatum. Clinical manifestations that occur from a hyperkinetic disorder, in particular reference to HD is marked by five specific features.		As previously mentioned, Huntington’s Disease is a [[#Hyperkinetic disorder\|hyperkinetic disorder]] which is caused by the degeneration of neurons in the cerebral cortex and striatum. Clinical manifestations that occur from a hyperkinetic disorder, in particular reference to HD is marked by five specific features.

	[[Image:Peripheral and Central Nervous System impairment in Huntington's Disease..JPG\|thumb\|right\|Symptoms and impairment of the human body that manifests in patients diagnosed of Huntington's Disease regardless of gender\|300px]]

	These are:		These are:
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	A diverse range of signs and symptoms can develop in those who are affected thus making symptoms clinically unique for different individuals. However, the typical symptoms that manifest in the majority of HD carriers are chorea and behavioural changes which occur at adult-onset between the ages 35-42.<ref name="PMID6451036"/><ref><pubmed>11442329</pubmed></ref> The progression of the disease continues to develop from the first signs of onset over 10-30 years, eventually leading to death.		A diverse range of signs and symptoms can develop in those who are affected thus making symptoms clinically unique for different individuals. However, the typical symptoms that manifest in the majority of HD carriers are chorea and behavioural changes which occur at adult-onset between the ages 35-42.<ref name="PMID6451036"/><ref><pubmed>11442329</pubmed></ref> The progression of the disease continues to develop from the first signs of onset over 10-30 years, eventually leading to death.

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2011-10-13T05:07:22Z

Clinical Manifestations

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	'''Behavioural/Psychiatric Disorder'''		'''Behavioural/Psychiatric Disorder'''

	Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>		Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref name="PMID11511702"><pubmed>11511702</pubmed></ref><ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>

	The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea.		The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea.<ref name="PMID11511702"/> However in recent studies it was found that those with [[#Juvenile-onset\|juvenile-onset]] cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>

	<ref name="PMID11511702"~~><pubmed>11511702<~~/~~pubmed></ref~~> However in recent studies it was found that those with [[#Juvenile-onset\|juvenile-onset]] cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>

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2011-10-13T04:59:53Z

Clinical Manifestations

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	Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>		Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>

	The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea. <ref name="PMID11511702"><pubmed>~~11232352~~</pubmed></ref> However in recent studies it was found that those with [[#Juvenile-onset\|juvenile-onset]] cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>		The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea.

			<ref name="PMID11511702"><pubmed>11511702</pubmed></ref> However in recent studies it was found that those with [[#Juvenile-onset\|juvenile-onset]] cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>

Z3290558 at 04:48, 13 October 2011

2011-10-13T04:48:54Z

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	Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>		Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>

	The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea. <ref name="PMID11511702"/></pubmed></ref> However in recent studies it was found that those with juvenile-onset cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>		The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea. <ref name="PMID11511702"><pubmed>11232352</pubmed></ref> However in recent studies it was found that those with [[#Juvenile-onset\|juvenile-onset]] cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>




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	<div id="Hyperkinetic disorder"></div>'''Hyperkinetic disorder:''' This type of disorders are characterised by excessive abnormal involuntary movements. Movements may be irregular, rhythmic, random, sustained or temporary and are commonly in the form of jerky movements or a tremor.		<div id="Hyperkinetic disorder"></div>'''Hyperkinetic disorder:''' This type of disorders are characterised by excessive abnormal involuntary movements. Movements may be irregular, rhythmic, random, sustained or temporary and are commonly in the form of jerky movements or a tremor.

			<div id="Juvenile-onset"></div>'''Juvenile-onset:''' Individuals who develop Huntington’s Disease symptoms before the age of 20.

	<div id="Linkage Analysis"></div>'''Linkage Analysis:''' Study aimed at establishing linkage between genes.		<div id="Linkage Analysis"></div>'''Linkage Analysis:''' Study aimed at establishing linkage between genes.

Z3290558: /* Clinical Manifestations */

2011-10-13T04:31:38Z

Clinical Manifestations

← Older revision		Revision as of 14:31, 13 October 2011
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	A diverse range of signs and symptoms can develop in those who are affected thus making symptoms clinically unique for different individuals. However, the typical symptoms that manifest in the majority of HD carriers are chorea and behavioural changes which occur at adult-onset between the ages 35-42.<ref name="PMID6451036"/><ref><pubmed>11442329</pubmed></ref> The progression of the disease continues to develop from the first signs of onset over 10-30 years, eventually leading to death.		A diverse range of signs and symptoms can develop in those who are affected thus making symptoms clinically unique for different individuals. However, the typical symptoms that manifest in the majority of HD carriers are chorea and behavioural changes which occur at adult-onset between the ages 35-42.<ref name="PMID6451036"/><ref><pubmed>11442329</pubmed></ref> The progression of the disease continues to develop from the first signs of onset over 10-30 years, eventually leading to death.












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	'''Behavioural/Psychiatric Disorder'''		'''Behavioural/Psychiatric Disorder'''

	Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold ~~which~~ may ~~involve~~ illnesses such as depression, apathy, obsessive-compulsive disorders and irritability <ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref>. Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and ~~may~~ be the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>		Behavioural changes in HD patients may be one of the most painful manifestations for the patient, family and friends to watch unfold. These changes may be caused by illnesses such as depression, apathy, obsessive-compulsive disorders and irritability.<ref><pubmed>11511702</pubmed></ref> <ref><pubmed>6221669</pubmed></ref> Just like the other manifestations of HD, behavioural changes may progressively become worse overtime, however in most cases, HD gene carriers will start to experience behavioural symptom changes before their official diagnosis and is said to be one of the earliest symptoms that arise. <ref><pubmed>12393306</pubmed></ref> <ref><pubmed>17481592</pubmed></ref>

			The severity of psychiatric disorders vary greatly between different patients with HD and is seen to have no correlation with dementia or chorea. <ref name="PMID11511702"/></pubmed></ref> However in recent studies it was found that those with juvenile-onset cases of HD were found to be psychiatrically more problematic. <ref><pubmed>17562929</pubmed></ref>

Z3290558: /* Glossary */

2011-10-13T03:59:26Z

Glossary

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	<div id="Endoplasmic reticulum"></div>'''Endoplasmic reticulum:''' Cellular organelle consisting of vesicular and cytoplasmic membranes that are involved in cellular transport.		<div id="Endoplasmic reticulum"></div>'''Endoplasmic reticulum:''' Cellular organelle consisting of vesicular and cytoplasmic membranes that are involved in cellular transport.

			<div id="Episodic memory"></div>'''Episodic memory:''' Memory in autobiographical events such as time, date, emotions felt in the past etc.

	<div id="Excitotoxin"></div>'''Excitotoxin:''' class of substances that damage neurons.		<div id="Excitotoxin"></div>'''Excitotoxin:''' class of substances that damage neurons.

			<div id="Executive function"></div>'''Executive function: ''' Umbrella term for cognitive processes which include functions involved with concentration, problem solving, planning, working memory, multi-tasking, initiation of actions and monitoring actions.

	<div id="Exon"></div>'''Exon:''' Sequence of amino acids in DNA that codes the information required for cellular protein production.		<div id="Exon"></div>'''Exon:''' Sequence of amino acids in DNA that codes the information required for cellular protein production.
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	<div id="Striatum"></div>'''Striatum:''' A subcortical part that is situated in the centre of the brain and is part of a larger system called the basal ganglia. It receives input from the cerebral cortex.		<div id="Striatum"></div>'''Striatum:''' A subcortical part that is situated in the centre of the brain and is part of a larger system called the basal ganglia. It receives input from the cerebral cortex.

			<div id="Subcortical dementia"></div>'''Subcortical dementia:''' Impairment in parts of the brain that are beneath the cortex. Usually includes changes in personality and attention span and a delay in initiation process of thinking.

	<div id="Teratogenicity"></div>'''Teratogenicity:''' The capability of inducing fetal malformations.		<div id="Teratogenicity"></div>'''Teratogenicity:''' The capability of inducing fetal malformations.

Z3290558: /* Clinical Manifestations */

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Clinical Manifestations

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 ==Clinical Manifestations==
-As previously mentioned, Huntington’s Disease is a [[#Hyperkinetic disorder|hyperkinetic disorder]] which is caused by the degeneration of neurons in the cerebral cortex and striatum. Clinical manifestations that occur from a hyperkinetic disorder, in particular reference to HD is marked by five specific features:
+As previously mentioned, Huntington’s Disease is a [[#Hyperkinetic disorder|hyperkinetic disorder]] which is caused by the degeneration of neurons in the cerebral cortex and striatum. Clinical manifestations that occur from a hyperkinetic disorder, in particular reference to HD is marked by five specific features.
 [[Image:Peripheral and Central Nervous System impairment in Huntington's Disease..JPG|thumb|right|Symptoms and impairment of the human body that manifests in patients diagnosed of Huntington's Disease regardless of gender|300px]]
 * Chorea movements
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 As HD is a neurodegenerative disorder, the cortex of the brain is affected thus naturally giving rise to the impairment in motor functions. Although there are a range of defective motor movements which may occur, chorea remains to be the one typically known to characterise HD. Derived from the Greek work khoreia which means dance, this involuntary movement typically involves an involuntary jerky dance like movement. [[#Motor impersistence|Motor impersistence]] is also very common in HD patients and is often classified under the same branch as chorea.<ref name="Clinical"/> The juvenile cases, individuals with a younger onset of HD may show symptoms of involuntary muscle twitching, abnormal eye movements, dystonia and parkinsonism which may be experienced rather than manifesting chorea.<ref><pubmed>10987900</pubmed></ref> Further down the track however, these involuntary movements will increase and become prevalent and spread to the arms, legs, trunk, and head of the patient and may develop into chorea. The individuals with an adult-onset of HD who start off with the symptoms of chorea, may develop an evolved complicated series of movements as the disease progresses which may include dystonia.<ref><pubmed>7753064</pubmed></ref>

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	[[File:HD patients.jpg\|right\|250px]]		[[File:HD patients.jpg\|right\|250px]]

	Huntington’s disease (HD) is an [[#Autosomal dominant\|autosomal dominant]] disease caused by the mutated huntingtin protein gene. HD is under the family of neurodegenerative diseases which only becomes identified by an expanded, repeated CAG trinucleotide tract, resulting in the formation of abnormal long proteins called polyglutamine seen at the molecular level.~~<ref name="~~PMID15459747~~"><pubmed>15459747</pubmed></ref>~~		Huntington’s disease (HD) is an [[#Autosomal dominant\|autosomal dominant]] disease caused by the mutated huntingtin protein gene. HD is under the family of neurodegenerative diseases which only becomes identified by an expanded, repeated CAG trinucleotide tract, resulting in the formation of abnormal long proteins called polyglutamine seen at the molecular level.{{#pmid:15459747\|PMID15459747}}

	HD is characterised by [[#Degeneration\|degeneration]] and dysfunction of the [[#Cerebral Cortex\|cerebral cortex]] and [[#Striatum\|striatum]] causing deterioration in neurons which may be the reason for its clinical manifestations in jerky, involuntary movements such as [[#Chorea\|chorea]].<ref><pubmed>21841917</pubmed></ref><ref><pubmed>21847326</pubmed></ref> HD was originally known as chorea before great detail of the disease was found, and in 1872, physician George Huntington first documented the clinical profile of the disease and HD was named after him.<ref name="PMID11232352"><pubmed>11232352</pubmed></ref>		HD is characterised by [[#Degeneration\|degeneration]] and dysfunction of the [[#Cerebral Cortex\|cerebral cortex]] and [[#Striatum\|striatum]] causing deterioration in neurons which may be the reason for its clinical manifestations in jerky, involuntary movements such as [[#Chorea\|chorea]].<ref><pubmed>21841917</pubmed></ref><ref><pubmed>21847326</pubmed></ref> HD was originally known as chorea before great detail of the disease was found, and in 1872, physician George Huntington first documented the clinical profile of the disease and HD was named after him.<ref name="PMID11232352"><pubmed>11232352</pubmed></ref>
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	'''HTT & normal functions:'''		'''HTT & normal functions:'''

	The HTT gene is comprised of 67 [[#Exon\|exons]] and is located between the markers D45127 and D45180 on the short arm 4th chromosome (4p) at position 16.3, spanning over a genomic region of over 200kb.<ref name="MM"><pubmed>20664076</pubmed></ref> The huntingtin protein is found in the nucleus, cell body, [[#Dendrite\|dendrites]] and nerve terminals and is also associated with cellular organelles such as golgi apparatus, [[#Endoplasmic reticulum\|endoplasmic reticulum]] and mitochondria. It is found in many body tissues but is predominantly active in the brain, specifically in the [[#Striatum\|striatum]] (integral part of basal ganglia). ~~<ref name="~~PMID15459747~~"/>~~		The HTT gene is comprised of 67 [[#Exon\|exons]] and is located between the markers D45127 and D45180 on the short arm 4th chromosome (4p) at position 16.3, spanning over a genomic region of over 200kb.<ref name="MM"><pubmed>20664076</pubmed></ref> The huntingtin protein is found in the nucleus, cell body, [[#Dendrite\|dendrites]] and nerve terminals and is also associated with cellular organelles such as golgi apparatus, [[#Endoplasmic reticulum\|endoplasmic reticulum]] and mitochondria. It is found in many body tissues but is predominantly active in the brain, specifically in the [[#Striatum\|striatum]] (integral part of basal ganglia).{{#pmid:15459747\|PMID15459747}}

	The precise function of HTT remains unknown. Many studies have tried to determine the pathological effects of HTT, with conclusion that it has a complex role at several cellular levels.		The precise function of HTT remains unknown. Many studies have tried to determine the pathological effects of HTT, with conclusion that it has a complex role at several cellular levels.
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	Individuals with CAG repeats of 27-35 in HTT gene do not develop HD; however their offspring is at high risk of developing the disease with CAG repeats of more than 35 in the HTT gene. <ref><pubmed>21601164</pubmed></ref>		Individuals with CAG repeats of 27-35 in HTT gene do not develop HD; however their offspring is at high risk of developing the disease with CAG repeats of more than 35 in the HTT gene. <ref><pubmed>21601164</pubmed></ref>
	CAG expansions are therefore the biomarkers used for genetic tests to identify mutant HTT carriers.~~<ref name="~~PMID15459747~~"/>~~		CAG expansions are therefore the biomarkers used for genetic tests to identify mutant HTT carriers.{{#pmid:15459747\|PMID15459747}}

	==Molecular Mechanisms & Pathogenesis ==		==Molecular Mechanisms & Pathogenesis ==
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	The accumulation of toxic HTT proteins with elongated polyglutamine chains impairs the calcium signalling pathway and disrupts cellular homeostasis and mitochondrial function. In transgenic mice with mutated HD, the mutated HTT has shown to trigger mitochondrial membrane permeabilization and [[#Apoptosis\|apoptotic]] cell death by impairing [[#Proteasome\|proteasome]] activity and interfering with calcium signaling. <ref><pubmed>11331615</pubmed></ref>		The accumulation of toxic HTT proteins with elongated polyglutamine chains impairs the calcium signalling pathway and disrupts cellular homeostasis and mitochondrial function. In transgenic mice with mutated HD, the mutated HTT has shown to trigger mitochondrial membrane permeabilization and [[#Apoptosis\|apoptotic]] cell death by impairing [[#Proteasome\|proteasome]] activity and interfering with calcium signaling. <ref><pubmed>11331615</pubmed></ref>

	Additionally, mutant HTT protein is also able to bind to the inositol 1,4,5- triphosphate receptor 1 (InsP3R1) on the [[#Endoplasmic reticulum\|endoplasmic reticulum]] and stimulate the inositol triphosphate (IP3) signalling pathway. The activation of the IP3 pathway leads to elevated calcium release from InsP3R1 of cells containing mutant HTT.~~<ref><pubmed>~~15336977~~</pubmed></ref>~~ Over time, this increase in cystolic calcium levels causes the mitochondrial calciumm intake to also increase, which eventually leads to mitochondrial swelling and the subsequent release of proapoptotic factors such as cytochrome ''c'' and [[#Apoptosis\|apoptosis]]-inducing factor.<ref><pubmed>18193642</pubmed></ref>		Additionally, mutant HTT protein is also able to bind to the inositol 1,4,5- triphosphate receptor 1 (InsP3R1) on the [[#Endoplasmic reticulum\|endoplasmic reticulum]] and stimulate the inositol triphosphate (IP3) signalling pathway. The activation of the IP3 pathway leads to elevated calcium release from InsP3R1 of cells containing mutant HTT.{{#pmid:15336977\|PMID15336977}} Over time, this increase in cystolic calcium levels causes the mitochondrial calciumm intake to also increase, which eventually leads to mitochondrial swelling and the subsequent release of proapoptotic factors such as cytochrome ''c'' and [[#Apoptosis\|apoptosis]]-inducing factor.<ref><pubmed>18193642</pubmed></ref>

	==='''Role in transcription inhibition'''===		==='''Role in transcription inhibition'''===
	The mutant HTT fragments are able to translocate into the nucleus where they most commonly interrupt DNA transcription or form intracellular inclusions.		The mutant HTT fragments are able to translocate into the nucleus where they most commonly interrupt DNA transcription or form intracellular inclusions.
	Studies have shown that unusually long polyglutamine tracts such as those in HD are able to disrupt normal function of [[#Transcription factor\|transcription factors]] and inhibit or alter DNA transcription.~~<ref name="~~PMID15459747~~"/>~~		Studies have shown that unusually long polyglutamine tracts such as those in HD are able to disrupt normal function of [[#Transcription factor\|transcription factors]] and inhibit or alter DNA transcription.{{#pmid:15459747\|PMID15459747}}
	Transcription factors such as p53, CREB-binding protein (CBP), specifity protein 1 (S1) and TATA-binding protein can bind to the polyglutamine chain of mutated HTT and inhibit RNA polymerase binding to the promoter region of the DNA strand. Several of the transcription factors such as CBP contain glutamine as part of their integral structure, which is able to interact with the polyglutamine chain on the mutant HTT protein and aggregate; hence repressing DNA transcription of specific proteins such as brain-derived neurotophic factor (BDNF).~~<ref><pubmed>~~12087131~~</pubmed></ref>~~ BDNF belongs to the neurotrophin family of growth factors found specifically in the hippocampus, cortex and basal ganglia. It functions to assist in neuron cell survival and also to support growth and differentiation of new neurons.<ref><pubmed>11408619</pubmed></ref>		Transcription factors such as p53, CREB-binding protein (CBP), specifity protein 1 (S1) and TATA-binding protein can bind to the polyglutamine chain of mutated HTT and inhibit RNA polymerase binding to the promoter region of the DNA strand. Several of the transcription factors such as CBP contain glutamine as part of their integral structure, which is able to interact with the polyglutamine chain on the mutant HTT protein and aggregate; hence repressing DNA transcription of specific proteins such as brain-derived neurotophic factor (BDNF).{{#pmid:12087131\|PMID12087131}} BDNF belongs to the neurotrophin family of growth factors found specifically in the hippocampus, cortex and basal ganglia. It functions to assist in neuron cell survival and also to support growth and differentiation of new neurons.<ref><pubmed>11408619</pubmed></ref>

	==Clinical Manifestations==		==Clinical Manifestations==
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	\|- align="center"		\|- align="center"
	\| Behaviour/Psychiatric		\| Behaviour/Psychiatric
	\| a progressive impairment in the cortex, however leading to behavioural disturbances and can vary depending on the severity and the degree of the state of disease. ~~<ref name="Clinical"/><ref name="~~PMID15459747~~"/>~~		\| a progressive impairment in the cortex, however leading to behavioural disturbances and can vary depending on the severity and the degree of the state of disease.{{#pmid:15459747\|PMID15459747}}
	\|- align="center" style="background:#eeeeff"		\|- align="center" style="background:#eeeeff"
	\|}		\|}