The molecular basis of life

Question 1

What causes alzheimer’s disease, in brief.

Answer 1

It causes neurons to die and the brain to shrink

Question 2

In what region is degeneration of the brain worse and what is the usual function of this region ?

Answer 2

Degeneration is worse in the hippocampus which is involved in learning and memory

Question 3

What comprises the characteristic neuropathology involved in AD

Answer 3

Plaques made of beta-amyloid

Question 4

What are plaque of beta-amyloid made of

Answer 4

Made of a degradation product of a large protein

Question 5

What is the protein degraded in the creation process of a plaque ?

Answer 5

The amyloid precursor protein

Question 6

To what can lead mutations in the amyloid precursor protein or in the enzymes that degrade it?

Answer 6

Can lead to inherited, early-onset AD

Question 7

How can we detect beta amyloid in the brain?

Answer 7

With modern imaging techniques

Question 8

Name one risk factor for developing AD

Answer 8

The ApoE4 allele of the ApoE gene

Question 9

What does AD disrupts, in brief?

Answer 9

disrupts brain networks that are involved in cognition

Question 10

What do we not know about AD?

Answer 10

• the normal function of the amyloid precursor protein
• We dont know how beta amyloid or amyloid plaques are related to the diseases
• we don’t know why Apoe4 is a risk factor
• We don’t know how the brain stores and retrieves memories
• we dont have treatment (preventive, reverse or ameliorate)

Question 11

Name some effective therapies that have been used without an understanding of the underlying molecular mechanism of action

Answer 11

-Dilantin for epilepsy
-opioids

Question 12

Why would a researcher study a rare disease with known molecular causes?

Answer 12

To gain insight into more common idiopathic disorders

Question 13

For what are responsible sodium channels and what do they do

Answer 13

for action potentials, which propagate along axons and enable neurons to communicate with each other

Question 14

What is a sodium channel in terms of molecular bio?

Answer 14

a large membrane protein

Question 15

What are the 9 sodium channel subtypes and their locations

Answer 15

• Nav1.1 - SCN1A : central and peipheral neuros
• Nav1.2-SCN2A : central neurons
• Nav1.3 - SCN3A: Embryonic neurons
• Nav1.4 - SCN4A: Adult skeletal muscle cells
• Nav1.5 - SCN5A : cardiac muscle celles, immature skeletal muscle celles, brain neurons
• Nav1.6 - SCN8A: central and peripheral neurons, main isoform at nodes of Ranvier
• Nav1.7 - SCN9A: Sympathetic neurons, DRG neurons, especially nociceptors
• Nav1.8 - SCN10A : primary nociceptors
• Nav1.9 - SCN 11A: Primary nociceptors

Question 16

What is Inherited erythromyelalgia (IE) ?

Answer 16

a rare, monogenic inherited disorder, characterized by episodes of redness and pain in the feet and hands. It can often be triggered by warmth or mild exercise.

Question 17

Where are almost exclusively expressed Nav1.7 sodium channels?

Answer 17

In peripheral nociceptors - they determines action potential treshold

Question 18

What causes IE

Answer 18

caused by mutations in the Nav1.7 sodium channel

Question 19

What causes the mutation of the Nav1.7 channel in IE?

Answer 19

it shifts the voltage-dependence of channel activation to more negative potentials (i.e., they make the channels more likely to open)

Question 20

What causes the mutation of nav1.7 that result in non-functional channels?

Answer 20

congenital insensitivity to pain

Question 21

So what kind of drug could be a specific and effective treatments for pain6

Answer 21

Drugs that selectively inhibit nav1.7 !!

Question 22

where does voluntary control of the limbs begins?

Answer 22

With commands from motor regions of the cerebral cortex.

Question 23

explain the pathway for controlling coluntary movements of the limbs

Answer 23

Neurons in motor cortex send axons to the spinal cord, where they synapse on spinal motor neurons that control voluntary movements of the limbs

Question 24

What can cause spinal cord damage in this case?

Answer 24

It can severs these corticospinal connexrions, cutting of communication between the brain and the spinal cord

Question 25

Which component of the peripheral and central NS can regenerate and which can’t?

Answer 25

Severed axons in the peripheral nervous system can regenerate
- axons in the central nervous system usually do not. we don’t know why.

Question 26

Name some potential strategies to restoring function in patients with spinal cord damage

Answer 26

• use brain activity recorded from motor cortex to guide a robotic limb
• transmit activity recorded in motor cortez to neurons in the spinal cord (a brain-spine interface)