Chapter 20: Neurodegenerative Diseases

Question 1

What is Parkinson’s disease?

Answer 1

Parkinson’s disease is a chronic, progressive neurodegenerative disorder. The primary symptoms are motor disturbances that result in a visible resting tremor and slowing of movement (bradykinesia). Other motor symptoms of the disorder include rigidity and postural instability.

Question 2

What is the primary pathology of Parkinson’s disease?

Answer 2

Pathology in PD is likely due to mitochondrial dysfunction and resulting oxidative stress. Additionally, protein aggregation in cells causes the formation of Lewy bodies, which trigger apoptotic cell death.

Question 3

Describe the effects of Parkinson’s disease on motor-control pathways.

Answer 3

Through the motor-control pathways dopaminergic cell loss in the substantia nigra results in decreased activation of the motor cortex by the thalamus.

Question 4

How is Parkinson’s disease treated?

Answer 4

The primary therapies increase DA signaling. They include:

1. L-DOPA
2. MAOIs
3. COMT inhibitors
4. DA agonists

Question 5

What is L-DOPA?

Answer 5

L-DOPA stands for levodopa. It is a metabolite of the amino acid tyrosine and is the precursor to dopamine, norepinephrine and epinephrine. L-DOPA crosses the blood-brain barrier and is synthesized into dopamine by the enzyme aromatic amino acid decarboxylase.

Question 6

What is Alzheimer’s disease?

Answer 6

Alzheimer’s disease is a chronic, progressive, dementia disorder. It cannot be diagnosed until postmortem. Therefore, for living patients it is diagnosed as mild or major neurocognitive disorder, possible Alzheimer’s disease, or probable Alzheimer’s disease.

Question 7

What is the primary pathology of Alzheimer’s disease?

Answer 7

The main cellular pathologies of Alzheimer’s disease are amyloid plaques, neurofibrillary tangles, and a significant loss of synapses.

Question 8

What are amyloid plaques?

Answer 8

Amyloid plaques form when beta-amyloid protein accumulates between neurons. These plaques cause pathological changes that result in neural degeneration.

Question 9

What are neurofibrillary tangles?

Answer 9

Neurofibrillary tangles are fibrous inclusions that are abnormally located in the cytoplasm of neurons. They are found in the entorhinal cortex, hippocampus and neocortex.

Question 10

How is Alzheimer’s disease treated?

Answer 10

Primary treatments are symptomatic and include:

1. cholinesterase inhibitors
2. NMDA glutamate receptor antagonist (modulator)

Question 11

What are the major neurodegenerative diseases?

Answer 11

1. Parkinson’s disease
2. Alzheimer’s disease
3. Huntington’s disease
4. ALS
5. MS

Question 12

What is Huntington’s disease?

Answer 12

Huntington’s disease (HD) is an inherited, single-gene, neurodegenerative disorder that leads to significant motor, cognitive, and psychiatric symptoms.

Question 13

How is Huntington’s disease treated?

Answer 13

No disease-modifying treatments are available for HD, but one drug, tetrabenazine, is approved for treatment of the excessive movement found in HD.

Question 14

How does tetrabenazine work to treat Huntington’s disease?

Answer 14

Tetrabenazine works by decreasing monoamine vesicle packaging, thereby reducing dopamine signaling. The decreased DA signaling, however, can bring about depressive and Parkinsonian side effects.

Question 15

What is ALS?

Answer 15

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder that affects motor function but spares most other cognitive and mood function.

Question 16

What is the primary pathology of ALS?

Answer 16

Degeneration of upper and lower motor neurons results in a progressive loss of motor function that generally starts with the far extremities and moves “inward” until muscles of breathing are finally affected. The mechanism of degeneration of the motor neurons (lateral corticospinal tract neurons) is still poorly understood but seems to involve protein aggregation in the cells and inflammation. These processes cause the triggering of apoptotic cell death pathways.

Question 17

How is ALS treated?

Answer 17

1. riluzole - has modest disease-modifying effects and may delay reliance on mechanical breathing support
2. radicava - a disease-modifying drug that slows progression of motor symptoms

Question 18

What is multiple sclerosis (MS)?

Answer 18

Multiple sclerosis is widely believed to be the result of an autoimmune attack on central nervous system myelin. Symptoms of MS vary widely and are largely unpredictable. Depending on the location of the immune attack, symptoms may include motor, sensory, gait, emotional, cognitive, or vision problems.

Question 19

What are the four subtypes of MS?

Answer 19

1. relapsing-remitting
2. primary progressive
3. secondary progressive
4. progressive-relapsing

Question 20

How is MS treated?

Answer 20

1. disease-modifying treatments

2. symptomatic treatments