Neurodegenerative Disease Therapy

Question 1

Neurodegenerative Disorders Main Characteristics (3)

Answer 1

LOSS OF NEURONS

GENETIC AND ENVIRONMENTAL FACTORS

AGGREGATION OF MISFOLDED PROTEINS

Question 2

3 Common Neurodegenerative Disorders

Answer 2

Alzheimers
Parkinsons
Amyotrophic Lateral Sclerosis

Question 3

Alzheimers protein accumulation

Answer 3

Beta-amyloid

Question 4

Parkinsons protein aggregate

Answer 4

alpha-synuclein

Question 5

Huntingtons protein aggregate?

Answer 5

huntingtin

Question 6

Four Main Stages of Alzheimers

Answer 6

Mild Cognitive Impairment
Mild
Moderate
Severe

Question 7

Pathology of Alzheimers (3)

Answer 7

Neuronal Degeneration and Cortical Atrophy

Neuritic Plaques

Neurofibrillary tangles

Question 8

Cholinergic Hypothesis of Alzheimers

Answer 8

DEFICIENCY OF ACH

degeneration of subcortical cholinergic neurons

consistent and early finding in AD

Question 9

Amyloid Hypothesis of Alzheimers

Answer 9

EXTRACELLULAR ACCUMULATIONS of beta-amyloid –> toxic to neurons

Question 10

Early Onset AD associated with two mutations

Answer 10

APP

PSEN1 and PSEN2

Question 11

Late Onset AD associated with presence of

Answer 11

epsilon4 allele of Apo-E

3 fold higher risk of deeloping AD

Question 12

APP encodes

Answer 12

beta-amyloid precursor peptides

Question 13

Tau Hypothesis of Alzheimers

Answer 13

HYPERPHOSPHORYLATION causes aggregates and forms neurofibrillary tangles

Question 14

Main Treatment of Cognitive Symptoms of AD

Answer 14

Cholinesterase Inhibitors

Question 15

Cholinesterase inhibitors MOA

Answer 15

reduce breakdown of ENDOGENOUS ACH

results in GREATER ACTIVATION OF POST-SYNAPTIC ACh

Question 16

Secondary Effects of Cholinesterase Inhibitors (4)

Answer 16

reduced tau phosphorylation

secretion of soluble APP

reduced beta-amyloid production

glutamatergic neurotransmission returns toward normal

Question 17

Donepezil

Answer 17

Cholinesterase inhibitor

long half life

Question 18

Rivastigmine

Answer 18

inhibits acetylcholinesterase and butyrylcholinesterase

TRANSDERMAL PATCH

Question 19

Galantamine

Answer 19

similar to donepezil

Question 20

Cholinesterase Inhibitor Side Effects

Answer 20

Salivation
Lacrimation
Urinary incontinence
Diarrhea
GI cramps
Emesis

Question 21

Memantine

Answer 21

GLUTAMATE RECEPTOR ANTAGONIST

long half

provides NEUROPROTECTION by REDUCING CALCIUM INFLUX AND GLUTAMATE INDUCED EXCITOTOXICITY

Question 22

Other Cognitive Treatment Strategies with no proof of improvement

Answer 22

Estrogen replacement
Vitamin E
NSAID’s

Question 23

Treatment of depression and anxiety in AD patients

avoid?

Answer 23

TRICYCLICS