Lecture 13: Huntington's Disease and Multiple Sclerosis Flashcards
(23 cards)
What is the prevalence of this disorder across different populations?
Generally higher in people of European descent
Endemic to all populations
What is the inheritance pattern of Huntington’s disease and what are the chances for offspring to inherit it?
Huntington’s disease follows an autosomal dominant inheritance pattern.
Each child of an affected parent has a 50% chance of inheriting the mutated gene.
What genetic mutation causes Huntington’s Disease, and how is it linked to disease severity?
Caused by a mutation in the HD gene on the short arm of chromosome 4.
Specifically, there are more than 36 CAG repeats in the gene sequence.
The higher the number of CAG repeats, the more severe the disease and the earlier its onset.
What does the HTT gene do?
It encodes the huntingtin protein, which is involved in nervous system development, BDNF production, and cell adhesion.
Is the normal function of huntingtin fully understood?
No, its normal function is not completely understood.
What kind of mutation occurs in Huntington’s Disease?
A toxic gain-of-function mutation (dotbienchucnangdochai) in the HTT gene causes the huntingtin protein to misfold(gapsai).
What is the key feature of the mutated huntingtin protein in Huntington’s Disease?
It has an expanded poly-Q region (too many CAG repeats), which causes the protein to clump together.
What happens to the mutated huntingtin protein in the nucleus?
It forms intranuclear inclusions and disrupts gene transcription.
What are the three major consequences of huntingtin aggregation in neurons?
Synaptic dysfunction
Mitochondrial toxicity and energy imbalance
Axonal transport impairment
What happens to the huntingtin protein in the cytoplasm?
It aggregates into toxic clumps, which impair protein recycling (proteostasis).
Where does the earliest and most severe neural loss occur in Huntington’s disease?
In the striatum, specifically the caudate nucleus and putamen.
In which brain cells is HTT (huntingtin) more highly expressed?
HTT is more highly expressed in neurons than in glial cells.
What brain structure shows progressive thinning and neuron loss in Huntington’s disease?
The cerebral cortex.
What happens to overall brain volume as Huntington’s disease progresses?
There is a general reduction in brain volume.
What does an MRI show in early Huntington’s disease?
Atrophy (shrinkage) of the caudate and putamen and enlargement of the lateral ventricles.
What are the motor symptoms associated with Huntington’s Disease?
Involuntary movements
Not repetitive or rhythmic
Dance-like movements
Difficulty walking
Severe motor impairment in later stages
What cognitive impairments are seen in Huntington’s Disease?
Can appear years before motor symptoms
Gradual decline
Affects attention, mental flexibility, planning, and emotion recognition
Late stages may resemble Alzheimer’s disease
How does Huntington’s Disease affect cognition, motor skills, and psychiatric health?
Striatal damage leads to tremors, poor coordination
Cortical atrophy affects memory, reasoning, executive function
Neurotransmitter disruption (e.g., dopamine) causes depression, anxiety, irritability
