7 - Inflammaging

Question 1

What are the inflammaging mecanisms of innate immunity? (3)

Answer 1

1) ↑ B-amyloid = NLRP3 activation = ↑ pro-inflamm CK = inflamasome
2) Impaired NK, DC, Neutro, Mono
3) ROS = NFkB cleavage = inactive forme = ↓ neuroprotection.

Question 2

What are the inflammaging mecanisms of adaptive immunity (2)

Answer 2

1) ↓ Ab producing cells (Bcells)

2) Impaired signal transduction from CD4/CD8 cells = ↑ memory cells + ↓ naive cells

Question 3

What are the genetic vs sporadic factors causing AD

Answer 3

Genetic : APP + presenelin 1/2 mutations

Sporadic : APOE4 allele + BDNFmet polymorphism

Question 4

Explain 3 molecular mecanisms causing AD

Answer 4

1) TREM 2 mutations result in soluble TREM2 = activate AKTGSK3 pathway = Microglia apoptosis
2) Ab plaques affect microglial function + cause toxicity that = neuronal death

↑ Ab bye : ROS, CK, APP cleavage,

3) Excitotoxic stress : Ab = i Glutamate intake in astrocytes = ↑ Glutamate = NMDA overactivation = ↑ Ca intake = ROS + C6 activation = neuronal death

Question 5

What are the therapis for AD (2)

Answer 5

Memantine = ↓ NMDA overactivation

Stem cell to regenerate neurons

Question 6

Name 2 molecular mechanisms found in AD & HD

Answer 6

ROS + inflammation/microglia dysfunction

Question 7

Différencier les signatures moléculaires précoces et tardives de MA + MH

Answer 7

Précoce : ↑ susceptibilité au stress cytotoxique (overexcitation)

Tardif : Resistance à la surexcitation

Question 8

What is the genetic cause of HD

Answer 8

HD mutation causing ↑ CAG repeats

Question 9

What parts of the brain are affected by HD

Answer 9

↓ Surtout striatum + ↑ Ventricules = ↓ environ 25% brain size

Question 10

Décrire les mécanismes moléculaire de HD

Answer 10

1) Inflamm + excitotox = Ca = ↑ C6 mitochondrial dysfct

2) C6 cleaves Mhtt = Toxic + altered trafficking + nuclear localisation = transcriptional dyst