L12 Huntington's Disease Flashcards
What is Huntington’s Disease
A familial neurodegenerative disease
Autosomal Dominant inheritance
What is autosomal dominant inheritance
The way a genetic trait or condition is passed down
One copy of mutated gene from parent
Men and women are equally likely
Motor Symptoms
Involuntary twitching
Excessive restlessness
Rigidity
Spasticity
Decreased Coordination
Voluntary movement abnormalities
Psychiatric Symptoms
Depression
Aggression
Antisocial behaviour
Irritability
Apathy
Impulsivity
Cognitive Symptoms
Problems planning and organising
Memory loss
Inattention
Dementia
Early Stage Huntington’s
minor involuntary movements
subtle loss in coordination
depression
irritability
Middle Stage Huntington’s
chorea
problems swallowing, balance, falls and weight loss
cannot sequence and prioritise
Late Stage Huntington’s
Non verbal, maintains comprehension
Chorea is replaced with dystonia, rigidity and bradykinesia
Speech Symptoms of Huntington’s
slower speech
Hypophonic and explosive speech
Voluntary control of lips, tongue and mouth declines
Intelligibilty of speech declines
What causes Huntingtons
Inherited trinucleotide repeat disorder, known as CAG
Most common repeat mutant gene
Primarily affects the brain
Explain the link between huntingtons disease and gene and proteins
Huntingtinn gene on chromosome 4, where CAG is repeated 30 times
Codes for Huntingtinns gene
What is Htt and what is it involved in
A mutation in Htt causes huntingtons disease
Responsible for:
-cellular transport
- protein processing
-synaptic vesicles
- transcription
-mitochondrial function
Neuronal Cell Death and Huntington’s
Impaired protein trafficking which interferes with synaptic transmission
Polyglutamate aggregation
Excitotoxicity
Oxidative Stress
Programmed cell death
What brain region is impacted in HD
Neuronal loss initially in striatum and spreads throughout basal ganglia and cerebral cortex
Huntingtinn protein aggregates
GABA neurons lost in striatum
What neurotransmitter pathways are impacted by Huntingtons disease
Degeneration of striatal GABAergic neurons can cause hyperactivity of dopamine systems
