Neurodegeneration 3 first half 2.0 Flashcards
(27 cards)
Main issue with current ND treatment?
Most ND have on cure, treatment only alleviates/delays symptoms
Main target of ND treatment?
Aggregates
Time course for an ND patient?
Usually over 50 with no evidence–> develop minor psychological/behaviour/motor issues–> develop memory loss, or issues with navigation–> begin differential diagnosis–> begin QOL treatments–>delay symptoms treatment–> alleviate symptoms–> palliative care–> death from another casue
Do ND kill people?
No, usually smthn like pneumonia
What is special about Wilsons Disease?
It can be treated
How does someone get Wilsons Disease?
Inherited–> genetic mutation
Main cause of Wilsons Disease?
Copper metabolism disease
Which protein is mutated in Wilsons disease?
Copper ion transporting P type ATPase (ATP7B)
Role of Copper ion transporting P type ATPase (ATP7B)?
Movement of copper ions across the membrane
Symptoms of Wilsons disease?
Abdominal pain, dark urine, jaundice, mood changes, rings around edge of cornea, tremor and stiff muscles
How is wilsons disease treated?
A copper chelator–> helps remove copper from the body
What are two copper chelators used to treat wilsons disease?
Penicillamine and trientine
What are the two ways that aggregates are targeted in ND?
Preventing their formation or causing their breakdown
What are causes other than aggregates that can cause ND?
Oxidative stress (toxic radicals–> e.g. superoxide)
Mitochondrial damage–> could produce cytochrome C
How is aggregate formation prevented?
Target parent protein, stimulate breakdown enzymes, prevent misfolding
How are aggregate parent proteins targeted?
Antisense RNA, genetic knockout (CRISPR-Cas9)
How is breakdown of aggregates increased?
Increases the action of the proteasome on that specific protein, use antibody treatments
Which disease could be treated with antisense RNA?
Huntingtons
Which protein is targeted by antisense RNA in huntingtons?
Huntingtin (HTT)
Which (failed) treatment of Alzheimers involved gamma secretase inhibitors?
Brought in a gamma secretase inhibitor to reduce the amount of beta amyloid being produced
How effective have antibodies against ABeta been in alzheimers?
Reduced cognitive decline by 20-40%
How are the antibodies for Azheimers treatment delivered?
Cannula infusion
How are alzheimers antibodies believed to work?
Recruitment of microglia
Main cause of PD?
Loss of dopaminergic neurons in substantia nigra in pathway to striatum
