Parkinson's Pathogenesis Flashcards
(43 cards)
What sex is more likely to get PD?
Male
What are the 3 types of PD onset?
Juvenile - before 20
early - 20-50
Late - after 50
What are 2 environmental risk factors?
Head trauma
Pesticide/herbicide exposure
What % of PD patients have a family history?
15 (5-10% have monogenic forms)
What 2 environmental factors can be protective in a dose-dependent manner?
caffeine
smoking
What are autosomal dominant PD?
Autosomal dominant mutations in SNCA (PARK1) & LRRK2 (PARK8)
What are autosomal recessive PD?
mutations in PRKN (PARK2), DJ-1 (PARK7) and PINK1 (PARK6)
What are genes resulting in mendelian forms of parkinsonism?
PARK genes
What does SNCA encode?
alpha-Syn that codes for protein alpha-synuclein
mutation on exon 4
What does SNCA have similiar clinical & pathological marks to?
idiopathic PD
What is SNARE complex responsible for?
fusion of NTs to synaptic membrane
Where is LRRK2 mutated?
G2019S mutation
Which patients is the LRRK2 mutation found in?
Later age onset
Idiopathic PD
What 4 functions is LRRK2 involved in?
Cell signaling
autophagy
Trafficking
mitochondrial function
What 3 things does increased LRRK2 kinase activity cause?
Impaired vesicle trafficking & lysosome function
Promotes neuroinflammation
What do LRRK2 alleles affect?
Neuroinflammation
What do WT LRRK2 variants play a role in?
Idiopathic PD
Where is the PRKN gene mutation found?
Chromosome 6
What 2 characteristics do PRKN mutations have?
Typical PD features
lower-limb dystonia
What 3 types of PD is PRKN gene mutation most common in?
Early-onset autosomal recessive PD
Sporadic early/late-onset
What 3 things is PRKN involved in?
Autophagy
Apoptosis
mitochondrial clearance
What 3 types of mutations are PINK1 mutations?
Point
frameshift
truncating
What type of PD does PINK1 mutations cause?
early onset recessive PD
What 4 mutations are DJ-1 mutations?
Missesne
whole exon deletions
frameshift
splice site
