NBL 444 Module 1 Exam - Common Themes Study Guides

What is aggregation?

protein clumping into larger insoluble structures

Why does aggregation tend to lead to insoluble structures?

the hydrophobic core of the protein becomes turned outwards due to the misfolding

What is aggregation?

protein clumping into larger insoluble structures

Why does aggregation tend to lead to insoluble structures?

the hydrophobic core of the protein becomes turned outwards due to the misfolding

What is the main issue caused by aggregation?

loss of function due to the lack of correctly folded proteins

How does aggregation apply to neurodegeneration?

If we can understand the structure of misfolded proteins and how the aggregation begins we can better understand a component of the pathology of a ND disease and how to possibly prevent it

What protein aggregates in HD and what are the characteristics?

Huntington; intranuclear inclusions and accumulation due to difficulty in digestion by proteasomes

What protein aggregates in AD and what are the characteristics?

amyloid β-peptide 1–40/1–42 and tau; extracellular (neuritic plaques) of amyloid beta and intracellular aggregates of tau

What protein aggregates in PD and what are the characteristics?

alpha-synuclein; Lewy bodies (inclusions in the cytoplasm of neurons) and Lewy neuritis (aggregates in neuritis)

What protein aggregates in prion disease and what are the characteristics?

prion protein; amyloid plaques similar in appearance to AD

What are prions?

pathogenic, misfolded proteins that have the ability to induce abnormal folding of proteins on normal variants of proteins

What causes prion diseases?

conformational change in the cellular prion protein, PrPC, to the misfolded form, PrPSc, PrPSc catalyzes more protein conversion resulting in the accumulation of the misfolded protein and being a template conformational change

Where do prions start in AD?

trans-entorhinal region

Where do prions start in PD?

the gut

What is stereotypical pathology?

the prevailing pattern of diseases and how they typically physiologically manifest

What is cross-seeding?

misfolded proteins recruit native proteins to form new aggregates that are released from the cell for uptake into other cells

Where is the highest burden of pathology seen in most ND cases?

brainstem and cerebellum

What protein aggregates in ALS?

TDP43

Which diseases show tau pathology?

AD, FTLD, CTE

What neurons are affected in ALS?

motor neurons in the spinal cord and brain stem and upper motor neurons in the motor cortex

What neurons are affected in FTLD?

large bipolar spindle-shaped von economo neurons

What neurons are affected in HD?

medium spiny GABAergic neurons in the striatum