Lecture 1 Flashcards
Neurodegenerative diseases
- Alzheimers/ dementia
- Parkinsons
- ALS/MND
- Multiple sclerosis
- Huntingtons (repeat expansion disorders)
- Spinal muscular atrophy – childhood form of motor neurone disease /don’t live beyond two years
2 main mechanisms for neurodegeneration
- Protein aggregation
- Mitochondrial dysfunction
Examples of Accumulation of protein
Beta amyloid and tau
Parkinsons in SN – alpha synuclein
polyQ- HD
Tdp43 – ALS/MND
Genetics
- HD autosomal dominant
- SMA autosomal recessive
- Rare familial cases early onset and sporadic in AD and PD
- Additional genetic risk factors e.g E4 allele of APoE-e4 8 times risk of AD
- Provides mechanism insight
- Generation of disease models – transgenic mouse
Parkinsons
Point mutation ins synuclein or too much can cause parkinsons
Lewi bodies- accumulation of alpha synuclein
Different forms of parkinsons
Parkinsons mechanism
- Mitophagy
- Lysosomal Degradation
What is the 2nd most common cause of ALS?
Sod1 mutation
ALS mutation
some abolish antioxidant function and some increase some do nothing
- destabalise the proteina and cause aggregation
Most common type mutations in ALS
intron non coding repeat expansion in C90RF72
FUS and TARDP (ALS)
RNA binding proteins next most common cause
what is significant about FTP and ALS ?
They overlap - see diagram
-Same mutations in same family can have different presentation due to overlapping spectrum
Mutation in TAU MAPT
– gives alzheimers and FTD
Therapies
- Drugs (AD & ALS)
- Antibodies (MS)
- Stem cells (MS & PD)
- Gene therapy – viral & AONS
Aricept
Aricept given to AD patients ingbitor or acetylcholine esterase to increase ACh - basal nucleus of minert full of cholinergic neurons depleted
AD brains have reduce Ach
Riluzole
treats ALS
