CAS NE 525 Study Guide - Summer 2018, Comprehensive Midterm Notes - Protein, Mitochondrion, Apoptosis
12 Oct 2018
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CAS NE 525
MIDTERM EXAM
STUDY GUIDE
Fall 2018
Parkinsons, ms, als, huntingtons, prions, alzheimers, FTD, down
Difference between FDG-PET or PiB PET.
All diseases except for MS have familial cases. Helps understand disease, proteins found to be
mutated in familial disease can SOMETIMES be the ones that affect sporadic cases
Ubiquitin is found in the proteasome
PET label for L-dopa in PD to see how many functional dopaminergic neurons are left that
would take it up
COMMON FEATURES and molecular pathways in Neurodegenerative diseases – loss of
function or gain of toxic function of certain proteins
Characteristics of Neurodegeneration: PROGRESSIVE, IRREVERSIBLE, NO
TREATMENT
Irreversible neuronal death: Neurons are post-mitotic cells, do not undergo cell
division after maturing into neurons.
o When neuron degenerates, astrocytes are swollen, creates post-ischemic lesion
(lack of blood flow, lack of oxygen, inappropriate metabolic activities, cell
death)
No treatment that can revert the disease. Must find a drug that is not symptomatic,
one that halts progression, reverses it, or prevents it
Seem to occur in the elderly (Alzheimer’s Parkinson’s) or earlier (20-30) for
Huntingtons, MS, ALS.
Methods of Diagnosis: Advantages and Disadvantages: DIAGNOSIS FOR ALL NEED TO
BE A COMBINATION OF THESE. The more we know about the biology the better we can
diagnose early
Identification of biological markers: for early detections, must know which are the
molecular pathways that become pathogenic
Behavioral/Neurological tests (PD, ALS, MS), Cognitive Tests (AD)
PET Scan: visualize damage by radio labeling molecules in areas particularly affected
in the disease. Problem: if damage seen with PET, might be already too late
o Ex: L-DOPA for PD (indicate how many dopaminergic neurons you still have,
less and less as disease progresses), B-amyloid for AD (more and more as
disease progresses)
MRI: evaluates changes in brain volume in specific areas, detect morphological
changes
o Ex: MRI in AD, enlargement of ventricles, shrinkage of brain areas;
subiculum and hippocampus
find more resources at oneclass.com
find more resources at oneclass.com
Different imaging techniques could detects different stages of the disease:
Example of AD – Stages, approach for each stage and detection of certain molecular
markers with each diagnostic approach
o Pre-clinical
o Mild cognitive impairment - MCI diagnosis
Amyloid PET: Amyloid b deposition, have these plaques even in
preclinical stage
o AD diagnosis
FDG PET (measures glucose uptake, metabolic activity), fMRI,
SPECT – Impaired synaptic function
MRI, MR-DTI – Atrophy, decreased white matter anisotropy
PET in AD and PD
Amyloid-binding molecules used in PET to follow progress of plaques in AD: the more
yellow/red, the more radioactivity, the more Abeta plaques, the more progressed the disease
Other molecules: REVIEW SLIDES 15,16
o PBR28, present as a response to plaques, they are immune cells that respond
to the inflammation, helps identify certain aspects of biology of disease.
Increase in PBR28 in AD localized to prefrontal cortex
o PiB: binds to plaques. Used to asses the efficacy of a therapeutic approach,
drug aimed at removing the plaques (bopineuzumab) – after 19 weeks of
treatment reduced uptake of PiB. Would you expect to see more or less
glucose activity? Don’t know.
PET scan in PD: Radioactive marker is L-DOPA. Less uptake of L-DOPA in Parkinson, less
light activation. Treat with L-DOPA, allows existing dopaminergic neurons to produce more
dopamine. Post-treatment shows more light activation in PET scans with radioactive L-DOPA
molecules
Allows to follow disease progression: progression through Hoehn & Yahr stages (1-
4). Less and less light activation with striatal F-Fluordopa marker through stages
Allows to evaluate neuronal integrity and functionality. FDG-PET - F-
Fluorodeoxyglucose uptake (glucose uptake, metabolic activity) is significantly
decreased in PD.
FDG-PET to trace metabolically active neurons (LIVING ONES) in AD: Advantage: used in
very early stages to detect decreased metabolic activity. WEAKER FDG-PET SIGNAL IN AD
MRI analysis
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Parkinsons, ms, als, huntingtons, prions, alzheimers, ftd, down. All diseases except for ms have familial cases. Helps understand disease, proteins found to be mutated in familial disease can sometimes be the ones that affect sporadic cases. Pet label for l-dopa in pd to see how many functional dopaminergic neurons are left that would take it up. Common features and molecular pathways in neurodegenerative diseases loss of function or gain of toxic function of certain proteins. Irreversible neuronal death: neurons are post-mitotic cells, do not undergo cell division after maturing into neurons: when neuron degenerates, astrocytes are swollen, creates post-ischemic lesion (lack of blood flow, lack of oxygen, inappropriate metabolic activities, cell death) No treatment that can revert the disease. Must find a drug that is not symptomatic, one that halts progression, reverses it, or prevents it. Seem to occur in the elderly (alzheimer"s parkinson"s) or earlier (20-30) for. Methods of diagnosis: advantages and disadvantages: diagnosis for all need to.
