Neurodegeneration

Question 1

what are some of the main clinical features of Parkinson’s disease

Answer 1

tremor 
rigidity
bradykinesia 
postural abnormality 
taste/smell disturbances 
difficulty with fine movement 
monotony of speech 
loss of balance 
depression

Question 2

what is the pathogenesis of Parkinson’s

Answer 2

decreased pigmentation in substantia nigra (function of this pigment isn’t known) which leads to motor features of Parkinson’s

Question 3

what is the biochemistry of Parkinson’s

Answer 3

reduction in caudate nucleus/putamen dopamine content

Question 4

what are the classes of drugs used to treat Parkinson’s and name examples of drugs in these classes

Answer 4

L-DOPA - given with cabidopa which is a DOPA DDC so prevents it being converted into dopamine in the periphery (dopamine can’t cross BBB but L-DOPA can)

dopamine agonists - bromocriptine. acts on D2 receptors

MAOIs

COMT inhibitors - tolocapone, entacapone. improve delivery of L-DOPA across BBB

Question 5

what are the drug classes used to treat Alzheimer’s and give examples

Answer 5

anti-cholinesterase 
only used in mild-moderate disease - stop working after 2 years
donepezil 
rivastigmine 
galantamine 

NMDA receptor blocker
memantine

Question 6

what are the risk factors for Alzheimers

Answer 6

age

genetic predisposition - APP, PSEN, ApoE

Question 7

what are the clinical symptoms of Alzheimers

Answer 7

memory loss
disorientation/confusion 
language problems 
personality changes 
poor judgement

Question 8

what is the Tau hypothesis for Alzheimers

Answer 8

tau proteins are soluble and in the microtubule of axons. The maintain the stability of microtubule complexes
Hyperphosphorylated tau is insoluble so it aggregates to form neurofibrillary tangles
These are neurotoxic and also result in microtubule instability

Question 9

what is the amyloid hypothesis for Alzheimers

Answer 9

amyloid precursor protein (APP) is cleaved by beta secretase (should be cleaved by alpha- secretase) and is then cleaved by gamma-secretase
this produces beta amyloid protein which aggregates together and forms fibrils with are deposited on neuronal cells and form plaques

Question 10

what is the inflammation hypothesis for Alzheimers

Answer 10

microglia become abnormal and their phenotype changes so that they attack normal neuronal cells
this is caused by increases in inflammatory mediators, increased phagocytosis of normal cells and decreased neuroprotective proteins