Theraputic Approaches to NeuroD. Disease Flashcards
Characteristics on NDD
Abnormal protein accumulation
Peferential death of certain neurons
Huntington's Disease Symptoms Pathophysiology - Lost Cells: - Expansion Treatment
Symptoms
- Chorea
- Altered basal ganglia
Pathophysiology
- Lost Cells: Medium spiny neurons in caudate & putamen
- Expansion of CAG
- Mutant huntingdon protein (toxic gain of function)
Treatment
- Tetrabenzadene = chrorea control
Alzheimer’s Disease
Symptoms
Failure in at least one of the following cognitive functions
- Language skills
- Visual spatial orientatation
- Spatial orientation
- Abstract thinking
- Judgement
- Cortical shrinkage
Alzheimer’s Disease
- Which cells lost?
- What accumulates?
- Neurons sensitive to neuron growth factor in the cortex, hippocampus, amygdala & cholinnergic basal forebrain neurons
- Loss of Ach
- Neurofibrillary Tangle and Amlyoid
What is in Neurofibrillay tangles?
- Tau protien that use to hold microtubles togethether
What is in Amyloid plaques?
- Amyloid Precursor Proteins cleaved by beta & gama secretase creates AB40/42
In what molecular structure is Gamma secretase located
- Lipid rafts
What physiological effect do amyloid plaques have?
- Altered axonal transport
- Altered synaptic activty
Alterd Ca2+ concentrations
Treatment options of Alzheimer’s Disease?
- Inhibit Acherase
- Small molecule inhibitors against amyloid plaques
- Statins to control choleestrol since gamma secretase is in a lipid raft
Syptoms of Parkinson’s Disease
- COnstant tremor
- Less spontanous movement
- Limb rigity
Parkinson’s Disease Pathophysiology
- Lose which cells
- What accumulates
- What is mutated
- Loss of dopaminergic neurons in substantia nigra
- Lewy Bodies accumulate
- Parkin & OCHL-1
What is in Lewy Bodies?
- alpha-synuclein * ubiquit
- failure to degrade proteinss
What is the role of Parkin & OCHL-1
Proteins involved in delivery of proteins to the proteosome
3 ways to prevent disease progression
gamma-secretase inhibitors
small molecule inhibitos
Abs directed at amyloid
3 ways to replace NT and which NT do you replaces
Implant dopamine secrting cell
Inhibit dopamine break down
Oral L-dopa & carbidopa
Why is L-dopa given with carbidopa
Carbidopa diven to relieve symptoms of excess dopamine & prevents peripheral dopamine causing side-effects
2 mechanisms to alter neuronal circutts
Partial palllidectomy
Deep brain stimulation
Why is a partial pallidotomy effective?
Reduce over activity of the globus pallidus
Where is DBS targeted
Subthalamic nucleus
Name 2 viruses used in attempt for gene therapy
Adenovirus & retrovirus
Name 2 neurotrophic factors that can be used to slow neuron loss with neurotrophic factors
- Neurotrophin
* Glial derived neurotrophic factor
Name 3 items that can be transplanted
- Embryonic dopamine producing cells
- Autografts, xenograft and gentically modified cells
- Stem cells
