Neurodegeneration Flashcards
(17 cards)
Necrotic Morphological Changes
Swelling, irregular membrane, then lysis and internal contents spill into EC space. Immune response causes inflammation which can be bad in NS
Excitotoxic Death (yielding 2 end results)
Initiated by stroke/necrosis, huge glut/Ca release. Act on neighboring NMDA Rs/Ca channels, leading to a huge influx of Ca. Mt release ROS and react w/ NO to produce peroxinitrites (very bad), and Ca activates lytic enzymes
Apoptosis Morphological Changes
Shriking/clumping, membrane bubbles off, get black whole, finally everything disperses as apoptotic bodies
Why We Don’t See Apoptosis in Adult Brains
Releases ATP as “find me” signal to macs/microglia, then 2nd “eat me” signal as phosphatidyl serine (normally on inside of membrane, flips it out)
Ischemic Core and Penumbra
Center of attack - necrotic and unsalvageable vs. Surrounding area - necrotic and apoptotic, what we’re trying to protect
Gross Changes from Traumatic Brain Injury
Huge ventricles and tissue atrophy
Tau Protein
Associated w/ MTs, gives them rigidity. Hyperphosphorylation destabilizes MTs, causing neuron to collapse into tangles
4 Stages of CTE Showing Tauopathy
Little subcortical pockets -> pockets growing -> a lot in cortex/cerebellum -> entire brain pretty much
Geographical Progression of Tau Deposition in AD
Starts in entorhinal cortex/hippocampus -> spreads to frontal cortex -> whole brain
Trans-Synaptic Spread of Tau Pathology
Seems that abnormal prot going through synapses: entorhinal cortex projects to frontal
3 Depositions: AD, Huntington’s, Parkinson’s
Amyloid-Beta Prot, Huntingtin, and alpha-Synuclein
2 Processing Pathways for Amyloid Precursor Protein (APP)
Alpha-secretase, producing a soluble fragment and small IC frag. Healthy
Beta-secretase - problematic one. Cleaved into ABeta frag, which is then cleaved by huge gamma-secretase complex into either ABeta40 or 42. 42 version causes problems
ApoE
Degrades ABeta stuff - ApoE2 or 3 is fine, ApoE4 can’t and so at higher risk for CTE/AD
Globular Intermediates of Proteins
Most toxic, damage synapses and how you get severe disease w/out deposits
2 Protein Degradation Pathways (major point)
Proteasome - ubiquitination. Abnormal prot might plug
Autophagy - goes wrong in Huntington’s
So deg diseases have problems w/ trashing prots
Diff b/w PrP and PrPsc
Morphological: Alpha helix vs. beta sheet
PrP Function
At synapse, binds ABeta-prot oligomers (40 or 42)
