NEURODEGENERATIVE DISEASES

Question 1

NAME NEURODEGENERATIVE DISEASE AND LOCALIZATION IN THE BRAIN

Answer 1

• ALZHEIMER’S DISEASE, cortex and hippocampus
• PARKINSON-S DISEASE, substantia nigra and cortex
• HUNTINGTON’S DISEASE, basal ganglia and striatum
• MULTIPLE SCLEROSIS, basal ganglia and brain stem

Question 2

COMMON PATHWAY OF NEURODEGENERATIVE DISEASE

Answer 2

• ALTERED DNA, transcript into altered RNA
• abnormal protein misfolding and aggregation
• creation of not solvable amyloid fibrillar aggregates
• they accumulate in the nerve causing neurofibrillary tangles, neurotoxicity, neuronal death

Question 3

treatment targets for ALZHEIMER DISEASE

Answer 3

• inflammation
• amyloid-beta
• tau proteins
• oxidative stress
• impaired autophagy
• abnormal cholinergic system function
• loss of nerve density (future therapy)

Question 4

APPROVED TREATMENTS FOR AD

Answer 4

• DONAZEPIL, target CNS and AChE, mild/moderate/severe AD, oral daily dose
• RIVASTIGMINE, target CNS selective+ ACE inhibitor, mild/moderate/severe AD
• GALANTAMINE, ACHE and aAChR activation by allosteric stimulation, mild/moderate AD
• MEMANTINE, NMDA antagonist, moderate/severe AD
• ADACANUMAB, Human anti-amyloid-beta, mild AD/mild cognitive impairment

Question 5

categories of Parkinson’s disease symptoms

Answer 5

• NA, loss of noradrenergic neurons-→ fatigue, irregular BP, decreased mobility, sudden drop in BP when standing
• DA, loss of dopaminergic neurons-→ tremor, stiffness, slow movements, impaired balance and coordination

Question 6

etiology of PD

Answer 6

alfa-synuclein aggregates (Lewy bodies), block DA release, accumulation of DA intracellular, DA CONVERTS TO ROS- reactive oxygen species, cytotoxicity and neuronal death.

Question 7

therapeutic strategies for PD

Answer 7

• drugs that increase level of dopamine in the brain
• drugs that help control non-motor symptoms
• drugs that affect other chemicals in the body (complementary improvements)

Question 8

GOLD STANDARD THERAPY FOR PD

Answer 8

• LEVODOPA, prodrug converted into DA, activates dopamine receptors
• INHALED CARBIDOPA, DA supplement
• INFUSION CARBIDOPA, stoma tube gel to the intestine via portable pump

Question 9

COMPLEMENTARY TREATMENT FOR PD

Answer 9

AIMS to reduce the breakdown of dopamine to increase the quantity at receptor level and increase the effect of dopamine remaining

Question 10

future therapies for PD

Answer 10

• neural transplant
• deep brain stimulation
• gene therapy, localize the faulty gene and replacing it with a more protective

Question 11

ETIOLOGY OF HUNTINGTON ‘S DISEASE

Answer 11

• GENE Ch4Ex1→ more than 35 CAG repetitions→ mutated HTT (huntingtin protein)→ protein misfolding → accumulation and neuron degeneration → GABAergic inhibitory signaling in the basal ganglia produces hyperactivity in the DA synapses→ enlargement of frontal horns of lateral ventricles and pathology manifestation

Question 12

HD TREATMENT

Answer 12

• TETRABENAZINE, inhibitor of vascular monoamine transporter (reduces DA storage)
• HALOPERIDOL, DA antagonist
• BACLOFEN, GABA beta receptor agonist
• SUPPLEMENTARY SUPPORT, antidepressant, mood stabilizers

Question 13

ETIOLOGY MULTIPLE SCLEROSIS

Answer 13

• VIRAL trigger (usually Epstein-Barr Virus)→ Tcell recruitment in the area of infection→ t cell release pro-inflammatory cytokines causing demyelination of the neuron→breakdown of neuronal signal → different area of localization

Question 14

TRADITIONAL MS TREATMENT

Answer 14

• GLATIRAMER, random polymer blocks immune response to myelin
• FINGOLIMOD, prodrug S1P receptors agonist
• BETAINTERFERON, IFN beta modifies immune response to virus

Question 15

ANTIBODY BASED MS TREATMENT

Answer 15

• ALEMTUZUMAB, humanized anti CD52 antibody on t and b cells
• NATALIZUMAB, integrin alfa 4
• ICRELIZUMAB, humanized anti-CD20 on B cells
• DACLIZUMAB, anti CD25 antibody, IL2R on T cells