more notes from Session Why and how specific neurons die in PD and what can be done about it?

 

Hirsch & Hunot, Lancet Neurol, 2009

  loss of 40% mice in SN foro

T lymoctypes producew neurodegeneration

CD4+ T cells

The deleterious effects of lymphosyltes involves fas/fas ligand

Brochard et al, J Clin Invest 2009

 

Brenner et al PLoS ONE 2008

injected mice with MPTP

 

 

——-

Animal models

Olsson

model of behavioural effects of dopamine depletion

understanding side effects of dopamine 

grwoth factor treaments

 

What’s wrong with the models?

modesl typically exhibit severs

many treatments that have worked in animals fail in clinical trials

fail in clinical trials

need monkeys

 

 

Angot et al 2010

maybe PD starts in gut or nose

poor sense of smell in >80% of PD cases

unclear when it begins but possible 2-5yrs before motor symptoms

F28 alpha-synuclein mouse —

too much in human mouse

progressive (with age) deficicit sense of smel (in many ways)

descriminate 

 

PREMOTOR SIGNS & other non-motor symptoms

collaboration with Roche

compound with DSS

perhaps if starts in the gut and then moves to the brain (~2-5yrs)

 

lashen lab

 

Another lab – HSPG

macropinocytosis

HSPG mediates aplha uptake

can inhibit this uptake

cell culture model

 

catherina prix Acta Neuropatho

systematic way to examine new compounds involved PD

gave it to PD mice

less a-s ( alpha-synuclein ) – prevent seeding

 

Injections of antibodeis against alpha-synuclein

 

Targetting PD with 

 

Model of slow degenetatin starting the neuron terminals are needed

 

Le Len, G; Alan Prochania JN – progressive loss of dopamine neurons in the ventral midbrain of adult mice heterozygote for engrailed1

 – also a Nature neuroscience

-slow and protracted loss

Bundin lab

now has these mice

terminal degeneration in the striatum

-degenerating

-regions specification terminal loss of function

 

See the engrailed1 (En +/-) mice – mitochondrial 

 

 

conclude

need more relevant animal models

–nothing about the pre-motor phase

slow degeneration (starting in terminals)

predictive of clinical success

 

prion like models

 

 

 

 

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