Neurodegenerative Disorders Flashcards
Examples of Neurodegenerative Diseases
- Alzheimer’s Disease*
- Parkinson’s Disease*
- Huntington’s Disease*
- Multiple Sclerosis
- Dementias
- Alper’s Disease
- Myotonia Congenita
- Creutzfeldt-Jakob Disease*
- Ischemia*
- Kennedy Disease
- Batten Disease
- Adie Syndrome
- Autism
- Cerebral Palsy
- Myopathy
- Pick’s Disease
- Bell’s Palsy
- Depression?*
- Epilepsy?*
Common Features of Neurodegenerative
Diseases
- Accelerated neuronal cell death resulting in a deficit or excess of specific neurotransmitters
- In many neurodegenerative diseases, affected regions of the brain contain intracellular and/or extracellular inclusions of misfolded proteins
- Ultimate causes of most are unknown
Potential Causes of Neurodegeneration
- Excitotoxicity
- Oxidative Damage
- Increased Apoptosis
- Inflammation
- Protein Misfolding & Aggregation
Excitotoxicity
Too much glutamate = highly toxic to neurons
Types of Glutamate Receptors
• Ionotropic
– AMPA =Na+ channel, depolarises neuron
– NMDA = Mg2+ block until depolarisation, Ca+2 channel
• Metabotropic
– Gq = releases Ca2+ from internal storage (ER)
Ca+2 & Neurotoxicity
• Ca+2 is necessary for neuronal function // if internal concentration gets too high, = causes neuronal death
• Activates proteases (calpains); lipases
= causes membrane damage
• Activates nitric oxide synthase & increases arachidonic acid release – contributing to oxidative stress and inflammation
Proposed therapeutic targets of ND
- Glutamate antagonists
- Calcium channel inhibitors
- Free radical scavengers
- Anti-inflammatory drugs (chronic)
- Protease inhibitors (suppress the action)
what is a neurodegenerative disorder
loss of structure/function of neurons - the death of neurons
what do alpha 2 adrenergic antagonists show
the strongest ability to suppress neuropathic pain
Apoptosis
programmed cell death - during development - getting rid of structures not required, neuronal cell remodeling
inappropriate activation of apoptosis
damage and death of neuronal cells
effective caspases
activation of series of caspase - break down proteins/DNA molecules
what do the intrinsic and extrinsic pathway converge on
converge on caspase 3
intrinsic pathway
cell recognizing excessive DNA damage = activate apoptosis regulated by proteins
TRIGGER: the release of Cytochrome C from mitochondria => APOPTOSOME - activates initiator caspase
extrinsic pathway
activated by T-cells of IS - express fast ligands on the surface - interact with adaptor proteins present on target cells - activated - trigger caspase 3
