Neurodegenerative disorders

Question 1

Alzheimer’s Disease

Answer 1

Loss of memory, cognitive function, language.

Amyloid precursor protein (APP) to form amyloid beta peptide. When misfolded it aggregates and forms plaques in the brain (extracellular).

Hyperphosphorylation of Tau - neurofibrillary tangles (intercellular).
Mutations in APP and Tau cause familial forms of AD. Most common is sporadic form (aging of brain).

Question 2

Parkinson’s disease

Answer 2

Impairment of fine motor control.
- Aggregation of alpha-synuclein (AS) protein forms insoluble fibrils which deposit as Lewy Bodies in dopaminergic neurons in the substantia nigra. Results in selective death of these neurons.

• Reduced availability to dopamine.
• Mutations in AS cause familial forms of PD. Brain aging most common (sporadic).

Question 3

Huntington’s Disease.

Answer 3

Mutation in Huntington gene results in expansion of CAG triplet repeats.

• results in polyglutamate repeats in abnormal HTT protein. Forms intramolecular hydrogen bonds, which eventually misfile and aggregate. Selective death of cells in basal ganglia cause the symptoms.

Question 4

Creutzfeldt-Jakob Disease.

Answer 4

Caused by misfolding of prion proteins.

Transmissible- infection by misfolded proteins converts normal proteins to misfolded form.

Belongs to Transmissible spongiform encephalopathies (TSEs)

Spongiform - appearance of infected brains, filled with holes resemble sponges.

Typical rule of thumb: if beta sheet structures form, proteins will aggregate.