neurological diseases: huntington's & parkinson’s diseases ...€¦ · anti-anxiety...
TRANSCRIPT
Neurological Diseases:
Huntington's & Parkinson’s diseases
07.25.2020
Andrés, Audrey, Daniel, and Joyce
Recap of last week
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● Progressive loss of structure or function of neurons
● Existing treatments can slow disease progression, but not stop or reverse it
● Examples:○ Huntington’s○ Parkinson’s○ Alzheimer’s○ ALS
Neurodegeneration
Movement in the brain
Key brain regions
striatum
substantia nigra
striatum
substantia nigra
Substantia nigraDopamine neurons
Normal brain
StriatumMedium spiny
neurons
Excitation Inhibition
Normal movement
Downstream motor pathway● Other parts of
basal ganglia● Thalamus● Spinal cord
Basic motor circuitry
Striatum in PD and HD
Huntington’s Disease (HD)
Symptoms of Huntington’s disease● Jerky, uncontrolled
movements (chorea)
● Cognitive deficits: problems with memory, planning, and abstract thinking
● Personality and emotional changes
● Anxiety, irritability, depression
~30,000 patients
More common in european ancestry
The striatum is usually the first brain region to lose neurons, specifically in the inhibitory pathway.
Pathology of Huntington’s disease
Striatum Atrophy of striatum
Substantia nigraDopamine neurons
Normal brain
StriatumMedium spiny
neurons
Excitation Inhibition
Normal movement
Downstream motor pathway● Other parts of
basal ganglia● Thalamus● Spinal cord
Substantia nigraDopamine neurons
StriatumMedium spiny
neurons
Uncontrolled movement
Huntington’s brain
Cause of Huntington’s disease
HD is hereditary. It is caused by an autosomal dominant mutation in the huntingtin gene.
Cause of Huntington’s disease
Normal Huntingtin:
Mutated Huntingtin:
NucleusNeuronal cell bodyAbnormal Huntingtin
...ACTGTGCTAGTCTAG CAG CAG CAG CAG CAG TAGCTTAG...
Progressionof Huntington’s diseaseSymptoms become worse as neuronal damage spreads to other brain regions such as the cortex.
Treatmentsfor Huntington’s diseaseSome drugs can treat the symptoms of HD:
● Tetrabenazine(reduces dopamine levels)
● Antipsychotic and anti-anxiety drugs
Gene therapy approaches to remove mutant huntingtin are being studied.
Parkinson’s Disease (PD)
Parkinson’s disease
● Motor deficits○ Tremors○ Rigidity○ Slurred speech
● Cognitive & emotional changes○ Depression○ Impaired thought○ Dementia
Symptoms of Parkinson’s disease
Prevalence of PD1 million patients in US, 10 million worldwide
Causes of Parkinson’s disease
● Much more complicated than Huntington’s!
● Genetic causes (15%)○ Mutations in one of many
genes can increase risk (Lrrk2, Park7, Pink1, etc)
● Non-genetic causes (85%)○ Combination of
environment and aging
Substantia nigraDopamine neurons
Normal brain
StriatumMedium spiny
neurons
Excitation Inhibition
Normal movement
Parkinson’s brain
Substantia nigraDopamine neurons
StriatumMedium spiny
neurons
Impaired movement
Downstream motor pathway● Other parts of
basal ganglia● Thalamus● Spinal cord
Effects of Parkinson’s disease
Cell death in substantia nigra reduces dopamine production
Dopamine
Substantia nigra
Several types of drugs can enhance dopamine signaling
Treatments for PD: Pharmacology
Treatments for PD:Deep brain stimulation
Questions?