General Neurodegenerative Mechanisms

Question 0

Mitochondrial Physiology

Answer 0

Fission || for effective transportation
Fusion || for content refreshing
Inner membrane || site of ion exchange and ATP synthesis
Cristae || nice grooves and folds, tons of oxygen

Question 1

Mechanisms

Answer 1

Mitochondrial dysfunction || apoptosis || proteostasis

Question 2

Lipofuscin

Answer 2

Concentration of oxidized fatty acids, lysosomal material

Used as a measure of oxidative stress

Question 3

Hypoxia

Answer 3

Lack /low levels of oxygen

Induces vacuolization in cristae so that electron micrograph shows empty spaces

Insult that predisposes mitochondria to second insult

Question 4

Apoptosis

Answer 4

Programmed cell death

Steps:
|| chromatin condensation (to inhibit transcription)
|| blebbing (pinching off of membrane as it implodes, reduces cytosolic volume)
|| phagocytosis

Question 5

Caspases

Answer 5

Molecular effectors of apoptosis
Require cleavage for activation
3 groups:
II. Actual effectors, DNA fragmentation
III. Cleave groups I and II to initiate their activity

Question 6

BCL2

Answer 6

Buffers levels of protein that releases cytochrome c from mitochondrial membrane to initiate endogenous apoptotic pathway

Question 7

Exogenous Apoptotic Pathway

Answer 7

Signal binding to extracellular domain activates intracellular Death Receptor domain that elicits downstream caspase 8 activity that then cleaves caspase 3 (effector)

Question 8

Endogenous Apoptotic Pathway

Answer 8

Aka mitochondrial, intrinsic apoptotic pathway
Activated in response to mitochondrial membrane dysfunction
Cytochrome c release from electron transport chain goes on to bind to caspase 9 to form apoptosome that later activates downstream effector caspases

Question 9

Proteostasis

Answer 9

Protein homeostasis

Equilibrium bw protein synthesis–folding–degradation

Sporadic: age dependent loss of proteins that regulate, protein modification on regulatory proteins

Familial: mutations on regulatory proteins

Question 10

Mechanisms Proteostasis

Answer 10

Ubiquitin Proteasome pathway (UPP)

Lysosomal pathway

Autophagy