Neurological Diseases Parkinson Flashcards
what are neurodegenerative diseases characterised by
progressive loss of neurons in specific regions of the cns
what are some examples on ndg d
mnd, parkinsons, alzheimers
what factor decides the effect that neurodegeneration has on the body
depending on the neurons affected
what are components of a neuron
dendrites, and axons, adittionally, myelinated neurons transmit signals faster
what are some neurotransmitters
acetylcholine
dopamine
serotonin
noradrenaline
glutamate
gamma amino butyric acid
how does depolarisation affect levels of calcium and sodium ions in a neuron at activation
sodium entry stimulates calcium ion influx via voltage dependant ion channels
what happens interneurally during synapse activation
vesicles fuse with plasma membrane and contents released into synaptic cleft
what function do reuptake transporters perform
uptake unused/unreceived neurotransmitters and repackage into vesicles
what other forms of nt control are used
enzymatic degradation
autoreceptors control release
what are glial cells
supporting cells outnumbering neurons
what are microglial cells
brainular macrophages
removes debris
defence
what are oligodendrocytes
formation of the mylin sheath
see oilgio, vs lipid rich mylin
what are astrocytes
dominant glial cell
forms blood brain barrier
provide nutrients
provide structural support
what is the prevalance of parkinsons
150k people in the uk
1% of over 60s
4% of over 80s
what are the clinical symptoms of parkinsons
tremour
postural instability
slowed movement and rigidity
what are some pathalogical hallmarks of pd
selective loss of dopominergic neurons
presence of aggregated protein
lewy bodies
where does selective loss of dopominergic neurons occur in pd
occurs in substantia nigra pars compacta
what does the snpc
controls movements(initiation and execution)
when do clinical symptoms occur
after 50-70 percent of neurons degraded
is there a distinction between famillial and sporadic forms of pd
no
what drives pd in familial cases
gene mutations
what is the ratio of familial to sporadic cases
<10:90
what are some hypothesises of pd pathogenesis
protien aggregation
mitochodrial dysfunction and free radical injury
what is a major constituent of lewy bodies
alpha synuclein
what is alpha synuclein
why does it clump
why is it linked to parkinsons
a presynaptic cytoplamic protien
stores and compartmentalises nt and maintains mitochondrial integrity
has a high amino acid composition which gives it a propensity to clump
mutations observed in genetic variants
what is the ibiquitin proteasome system
responsible for the destruction of protiens
what are the two stages of ups
covalent attachment of ubiquitin to substrate
degradation by proteosome
why is ups linked to parkinsons
mutations observed in a protien for ubiquiten ligase
why is mitochondrial dysfunctioin linked to parkinsons
postmortem tissue finds high levels of lipid peroxidation oxidation of proteins and lower glutathione levels
what specific part of the mitochondrial process is linked to parkinsons
dysfunction and inhibition of complex 1 activity in electron transport chain
leading to higher levels of ros
which drug caused mitochondial dysfunction in drug addicts
mptp caused death of substancia nigra pars compact no lewy bodies
crosses the bbb
converted into neurotoxic metabolites by astrocytes
what environmental factors are linked to inhibition of complex 1
pestecides
what is pink 1
mitochondrial protien with kinase activity
protects for oxidative stress
neuroprotective
targets damaged mitochondria for degredation
what is dj 1
function is under debate
multifunctional
neuroprotective
antioxidant?
reduced activity led to cell death
what drugs are used to manage pd
dopaminergic drugs
levodopa (dopamine precursor converted by dopa decarboxylase)
in combination with dopa decarboxylase inhibitor
increases duration and requires less
reuptake inhibitor
what is mao and what does its inhibition lead to and whats a drug used
a neurotransmitter protease
increases dopamine
selegiline
what is bromocriptine
a dopamine receptor agonist
