protein misfolding

Question 1

Alzheimer’s disease

Answer 1

amyloid beta peptitde (4.2 kDa) released into extracellular space

• misfolding/aggregation of AB forms soluble oligomers and insoluble plaques (extra cell deposits)
• tau –> hyperphos. and form neurofibrillary tangles (intracell)
• located to language and memory centers in the brain

Question 2

Parkinson’s disease

Answer 2

• selective loss of dopaminergic neurons in PD (substantia nigra)
• caused by a-synuclein - cytosolic and bound to PM
• insoluble fibrils deposit as Lewy bodies in substantia nigra, reduced availability of dopamine
• tremors, rigidity or stiffness, slow movement, difficulties speech balance and coordination, progressive worsening
• dopamine replacement therapy and deep brain stimulation

Question 3

Amyoptropic Lateral Sclerosis (ALS)

Answer 3

• copper zinc superoxide dismutase (CuZn SOD)
• cytosolic enzyme responsible for dismutation of superoxide anion to hydrogen peroxide
• mutations of SOD cause Gain of function, form ROS and induces oxidative stress
• activates cell death pathways
• nerve cells in brain and spinal cord, loss of muscle control, muscle twitching and weakness or slurred speech

Question 4

Huntington’s diease

Answer 4

HTT (huntingtin protein), localized in cytosol and nucleus

• important role in nerve cells in the brain and is essential for normal development before birth
• CAG trinucleotide repeat, expansion of CAG repeat leads to HD
• CAG codes for glutamine, polyglutamine repeats in abnormal huntingtin protein, forms misfolding and aggregates