Parkinson's Flashcards
What are the pathological hallmarks of Parkinson’s?
Profound and selective loss of dopaminergic neurones
Presence of intra-neuronal inclusions (Lewy Bodies)
(Diagnosis of PD can only be confirmed post-mortem)
Where does dopaminergic neurone cell death occur?
SNpc
What are the three hypotheses for PD pathogenesis?
Protein aggregation (Lewy Bodies) Free radical injury (oxidative stress) Mitochondrial dysfunction
What are Lewy bodies?
Intracellular (cytoplasmic) inclusions formed from the accumulation of aggregated protein
What Lewy bodies’ major constituent?
Alpha-synuclein (a pre-synaptic protein)
What does alph-synuclein have a high propensity to aggregate (ie mutate)?
Due to its amino acid composition
What is UPS?
Ubiquitin-proteosome system, responsible for the destruction of damaged proteins
What effect does a mutation in Complex I of the electron transfer chain have?
Disrupts electron transfer, ROS production enhanced, less ATP production
What effect does a loss of function mutation in PINK-1 have?
Mitochondria dysfunction, more susceptible to oxidative stress, loss of neurones
What is PINK-1?
A mitochondrial protein with kinase activity. Helps protect from oxidative stress, helps maintain mitochondrial integrity
What is DJ-1?
A multi-functional protein, neuroprotective, antioxidant
What is PD treatment centred on?
Restoring dopamine
What is the first line of treatment and what is it given in combination with?
L-Dopa (a dopamine precursor) with a peripheral dopa decarboxylase inhibitor eg carbidopa
