BIOM30002 Lecture Notes - Lecture 32: Copy-Number Variation, Thioflavin, Synuclein
Document Summary
Stage 5: temporal neocortex (memory and language, sensory association and premotor areas) Stage 6: neocortex; primary sensory and motor areas. Diagnosis is typically delayed until stage 3, further implying a long preclinical period of neuronal decline. Natively unfolded so aggregates if left in a test tube. Thioflavin t fluoresces when it finds lots of beta sheets. Beta sheets associated with amylogenic proteins (like alpha-syn which aggregates and forms amyloid over time) Forms long fibrillar structures which deposit in neuron - toxic species could form along this pathway. Via copy number variation of a-synuclein gene (overexpression of protein due to duplication or triplication) Nacl control shows no tioflavin t fluoresence because no aggregation. Some metals (al, cu, fe) brings it off baseline much earlier and increases overall amount of aggregation a-synuclein and dopamine. The substantia nigra is significantly affected in pd. Substantia nigra neurons have a high concentration of dopamine. Dopa(cid:373)i(cid:374)e i(cid:374)du(cid:272)ed -synuclein oligomers are not thioflavin t reactive.
