neurological diseases: huntington's & parkinson’s diseases ...€¦ · anti-anxiety...

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

Treatments for PD:Deep brain stimulation

Questions?