The molecular basis of life Flashcards
(27 cards)
What causes alzheimer’s disease, in brief.
It causes neurons to die and the brain to shrink
In what region is degeneration of the brain worse and what is the usual function of this region ?
Degeneration is worse in the hippocampus which is involved in learning and memory
What comprises the characteristic neuropathology involved in AD
Plaques made of beta-amyloid
What are plaque of beta-amyloid made of
Made of a degradation product of a large protein
What is the protein degraded in the creation process of a plaque ?
The amyloid precursor protein
To what can lead mutations in the amyloid precursor protein or in the enzymes that degrade it?
Can lead to inherited, early-onset AD
How can we detect beta amyloid in the brain?
With modern imaging techniques
Name one risk factor for developing AD
The ApoE4 allele of the ApoE gene
What does AD disrupts, in brief?
disrupts brain networks that are involved in cognition
What do we not know about AD?
- 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)
Name some effective therapies that have been used without an understanding of the underlying molecular mechanism of action
-Dilantin for epilepsy
-opioids
Why would a researcher study a rare disease with known molecular causes?
To gain insight into more common idiopathic disorders
For what are responsible sodium channels and what do they do
for action potentials, which propagate along axons and enable neurons to communicate with each other
What is a sodium channel in terms of molecular bio?
a large membrane protein
What are the 9 sodium channel subtypes and their locations
- 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
What is Inherited erythromyelalgia (IE) ?
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.
Where are almost exclusively expressed Nav1.7 sodium channels?
In peripheral nociceptors - they determines action potential treshold
What causes IE
caused by mutations in the Nav1.7 sodium channel
What causes the mutation of the Nav1.7 channel in IE?
it shifts the voltage-dependence of channel activation to more negative potentials (i.e., they make the channels more likely to open)
What causes the mutation of nav1.7 that result in non-functional channels?
congenital insensitivity to pain
So what kind of drug could be a specific and effective treatments for pain6
Drugs that selectively inhibit nav1.7 !!
where does voluntary control of the limbs begins?
With commands from motor regions of the cerebral cortex.
explain the pathway for controlling coluntary movements of the limbs
Neurons in motor cortex send axons to the spinal cord, where they synapse on spinal motor neurons that control voluntary movements of the limbs
What can cause spinal cord damage in this case?
It can severs these corticospinal connexrions, cutting of communication between the brain and the spinal cord
