Neurodegeneration Flashcards
How is the spread of neurodegeneration like?
prion-like “spread”
Which protein aggregates in Parkinson? How is the aggregation spreading?
alpha-Synucleine: spread starts in brain stem and olfactory bulb and progresses over the frontal lobe throughout the brain until almost all the brain is affected –> voluntary but not involuntary movement
Which protein aggregates in Amyotrophic lateral sclerosis (ALS)? How is the spread?
TDP43 spreads. Spread starts in motor cortex which leads to paralysis and speech impairment –> spread to the front of the brain and brain stem
Describe the long pre-morbid phase in Neurodegenration
years:
-20: constipation
-10: sleep disorder, Depression
0: pain, fatigue, tremor
10-20: dyskineasia, urinary symptoms, falls, postural instability, posychosis
How does alpha.synuclein accumulate in parkinson?
healthy: monomer form nucleus which form protofibrils which then form fibrils-
pathology: nucleus can aggregate or the fibrils undergo secondary nucleation via surface catalysis or fragmentation which leads to the formation of oligomers
Name examples for neurodegenartive diseases
spinocerebellar ataxias
atypical parkinson syndromes
huntington disease
ALS
Spinal muscle atrophy
Alzheimers
Name neuromuscular and motorneuron disease
ALS
spinal muscular atrophy
describe the pathology oif spinal muscle atrophy
normal individual: SMN1 mRNA has all exons (1 -8)
and SMN2 mRNA has exons 1-8 but 7 (exon skipping)
pathology: SMN1 gene is completly missing. Only SMN2 gene is functional but due to exon 7 skipping the protein is truncated
How does gene therapy (nusinersen) work in spinal muscular atrophy
a small ASO (=short oligonucleotide) removes block from intron 7 –> exon 7 not blocked/skipped
How does the prognosis of ALS correlate with affected regions?
The more regions affected in the brain the more agressive (more symptoms) the progression the worse the prognosis
