Neurodegeneration Flashcards
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
