14

Question 1

Similarities b/w Notch and APP

Answer 1

• pathways rely on the same proteolytic machinery= secretase
  (alpha, NICD) and beta, AICD)
• both have y-sercetase activity
• Notch signalling is crucial for development, - APP misprocessing is linked to neurodegeneration

Question 2

APP’s roles ?

Answer 2

plasticity,
synapse formation,
iron export,
anterograde transport
(AICD may regulate Ca2+)

Question 3

which Sheddases act on APP?

Answer 3

beta & gamma secretases act on APP

Question 4

Tau and AD?

Answer 4

Tau gets hyperphosphorylated forming tangles

Question 5

What are Gingipains? (AD)

Answer 5

They are extracellular Cysteine proteases that:

-alter host immune response
-deregulate signaling pathways
-induce anoikis/apoptosis
-triggers tissue destruction, cleaves Tau
-breaks down normal brain proteins

Question 6

AB (1-42) and its contradictions?

Answer 6

Aβ(1–42) is a major component of amyloid plaque

HOWEVER

-Aβ(1–42) is anti-microbial!

Question 7

Sugar Hypothesis and AD ?

Answer 7

Glucose consumption:

-brain uses ~60% of all glucose you consume
-inability to metabolize glucose could lead to cognitive impairments
-Ab destroys insulin receptors!
Brain is craving the glucose but can’t respond to it

Question 8

Diabetes, GSK-3 and AD correlation

Answer 8

In diabetes, GSK3 cannot be inhibited by AKT & it phosphorylates Tau (seen in AD)

Question 9

What is a Semaglutide?

Answer 9

GLP-1 receptor agonist- used for type 2 diabetes and weight management.

Question 10

what is IRS and its role?

Answer 10

IRS is an adaptor protein involved in insulin and IGF (Insulin-like Growth Factor) signaling.

IRS acts as a bridge between the insulin receptor and PI3K, leading to glucose uptake, metabolism, and growth signaling.

Question 11

Alpha cells make —- and Beta cells make —-

Answer 11

Alpha = Glucagon
Beta = Insulin

Question 12

What amino acid is needed for disulfide bonding?

Answer 12

cystine (-SH )

Question 13

What is the avg blood glucose level?

Answer 13

~5mM
** this spikes after a meal to initiate insulin secretion

Question 14

How do b-cells respond to Glucose?

Answer 14

• rIse in glucose activates GLUT transporter
• Glycolysis and OXPHOS converts glucose to ATP
• ATP close K+ channel
• Depolarization activates Voltage-senstivie ca2+ channels
• Increase intracellular Ca2+ levels trigger exocytosis of insulin

Question 15

IRS and its domians

Answer 15

PH domain (binds to RTK)
PTB domain (binds to RTK + PI3K + Grb2)

Question 16

Insulin Signaling Pathway via AKT (PKB)

Answer 16

PDK1 & AKT PH domains permits phosphoinositide binding

binding of PIP3 and PDK1 activates AKT (PKB)

AKT phosphorylates and inactivates GSK3

Glycogen Synthase is dephosphorylated
(glycogen synthesis )

**when GS is phosphorylated = Less glycogen made

insulin causes more glucose to enter liver cells

pathway leads to glucose conversion to glycogen for storage

AKT pathway favours protein synthesis and survival

Question 17

What do Insulin and Glucagon to to glycogen in the cells?

Answer 17

Insulin promotes glycogenesis,
(glucose –> glycogen for storage)

Glucagon promotes glycogenolysis, (breaking down glycogen into glucose to increase blood glucose levels)