Neuordegeneration diseases

[Aaron1991]

Hey!

 

So I've to write a 2000 word essay on the similarities and differences between Huntington's and Parkinson's regarding 'molecular pathology'.

 

However, I've driving myself mad trying to understand this - given that there is so much information out there on these two disorders.

 

I know I've to at least talk about the genes involved, CAG repeats, and Ubiquitin.

 

Can anyone explain briefly to me where the difference and similarities actually lie between these disorders?

 

Thanks

[Elite Engineer]

One similarity between the two is that the genetic mutation alters dopamine neuron activity, owing to the muscular movements. A difference between the two (and this is very general..not enough room/time to go into depth) is how the mutation effects the dopamine neurons.

 

In Huntington's Disease: Early in the disease (known as the hyperkinetic state), there is an increase on dopamine neuron activity, which causes abnormal muscular movements. In later stages, there is less dopamine activity.

 

In Parkinson's Disease: There is a general reduction in dopamine neuron activity, causing the abnormal muscular movements.

 

IMO, I would write majority of the paper discussing the sim/diff. in the genetic mutation itself..you can really go deep into that kind of discussion. Then summarize the effects on the body. Hope this helps.

 

~EE

[Xalatan]

Both diseases involve the basal ganglia controlling motor programs and movement. With PD, there is a loss of dopaminergic neurons in the substantia nigra, leading to cogwheeling rigidity and pill rolling tremor etc. In Huntington's, there is a loss of basal ganglial GABAergic neurons through CAG triplet expansion leading to chorea and neuropsyhiatric complications.

[Function]

A picture says more than 1000 words .. Are you familiar with the basal ganglia and their effects on one another? It may be very interesting to draw a scheme displaying effects (excitatory vs. inhibitory) of:

• Amygdala
• Neostriatum: striosomes & matrix
• Substantia nigra
  • Compact part
  • Reticular part
• Globus pallidus, external part
• Globus pallidus, internal part
• Subthalamic nucleus of Luys
• Ventral anterior and ventral lateral nuclei of thalamus
• Intralaminar nuclei of thalamus
• Prefrontal cortex, primary motor cx, parietotemporal cx
• (Optionally, superior colliculus and pedunculopontine nuclei)

on one another. We saw such a scheme and I memorised it and can still reproduce it. It is then very handy to distinguish a direct pathway from an indirect pathway in the basal ganglia (look it up), and the role of D1 and D2 dopamine receptors in these pathways, consequently describing the effects of dopamine on these pathways and, eventually, excess/deprivation of dopamine.

 

 

This is the scheme we were supplied by our neuroanatomy professor. Try to distinguish the direct from indirect pathway (look it up) and role of D1 and D2 and where things go wrong in HD and PD.

Edited April 4, 2016 by Function

[Aaron1991]

Thanks for the replies!

 

I don't need to know too much about the actual brain areas thought.

 

I'm really just having trouble focusing my essay atm. I've written about Huntington's - CAG repeat expansion, protein aggregation/accumulation, and how aggregated disrupt UPS function (not sure how), allowing the aggregates to build up and damage or kill the cell.

 

However, Parkinson's is confusing me. Is the UPS even involved here? Where do Lewy bodies even come from? I know in Huntington's the aggregates come from the overly long htt proteins being cut up into filaments, which then all accumulate into one. With Parkinson's however, I can't find much on where these inclusions come from.

 

(wrote this really fast, so hope it makes sense)

Edited April 4, 2016 by Aaron1991

[Function]

If I recall correctly, UPS is indeed involved in it (and disturbed); there are many factors causing PD; Lewy bodies are aggregations of synuclein-alpha proteins, try to look a bit further into that matter too

 

if I have any time these days (very short on time now), I might try to look up the pathogenesis of PD again in my neurophysiology course slides .. due when is your essay?