Cellular mechanisms of neurological disease Flashcards
What are the 3 types of proliferative capacity of cells?
Permanent cells
Stable cells
Labile cells
What type of cells are glial cells in terms of their proliferative capacity?
Labile cells
Which type of cell death causes an inflammatory response?
Necrosis
List 4 key causes of cell necrosis.
Ischaemia / hypoxia
Toxins
Trauma
Infections
In necrosis, what happens to the size of cells? Why is this?
Increase in cell size due to the influx of water and ions because of the breakdown of the plasma membrane
Describe the intrinsic pathway of apoptosis.
Pro-apoptotic proteins BAX and BAK insert into the mitochondrial membrane
This causes cytochrome c to leak out of the mitochondria into the cytoplasm
Cytochrome c in the cytoplasm activates caspase-9, triggering activation of the caspase cascade
Describe the extrinsic pathway of apoptosis.
Death receptors on the cell surface (Fas) are activated by binding with their ligands (FasL)
Death receptors have intracellular death domains
When activated, death domains bind with adaptor proteins, which activate the caspase cascade
What is a common death receptor found in the extrinsic pathway of apoptosis?
Fas
In the extrinsic pathway of apoptosis, the intracellular death domain binds with what in order to activate the caspase cascade?
Adaptor proteins
In relation to the extrinsic pathway of apoptosis, FasL is expressed on what?
Activated T lymphocytes
What does Wallerian degeneration cause?
Degeneration of the distal axon and myelin
Define transneuronal degeneration.
When a neuron degenerates due to damage in a connected neuron, rather than direct injury to itself
Via which process are ROS generated and where does this take place?
Oxidative phosphorylation in the mitochondria
What is the most reactive and damaging ROS?
Hydroxyl radical (OH-)
List 3 enzymes which manage ROS levels.
Superoxide dismutase
Catalase
Glutathione peroxidase
What 3 ways do ROS cause cell injury?
Lipid peroxidation - damages cell membranes
Protein damage - disruption of cellular processes
DNA damage - triggers apoptosis
In which 3 ways would mitochondrial membrane damage lead to cell injury?
Dysfunction
ROS production
Apoptosis
How would lysosomal membrane damage lead to cell injury?
Release of proteolytic enzymes
In which 4 ways would plasma membrane damage lead to cell injury?
Loss of stable resting membrane potential
Loss of osmotic balance
Loss of cellular constituents
Increase in cytosolic calcium
An accumulation of misfolded proteins in a cell can trigger which response?
Unfolded protein response
The unfolded protein response brings about which 2 key actions?
Slows protein translation
Increases chaperone production
What are misfolded proteins referred to as when they are intracellular?
Inclusions
What are misfolded proteins referred to as when they are extracellular?
Plaques
Excitotoxicity causes neuronal cell death via the influx of which ion?
Calcium
Polioencephalitis affects which kind of brain matter?
Grey matter
In astrocytosis, astrocytes increase their expression of which protein?
Glial fibrillary acidic protein (GFAP)
List 3 trophic factors secreted by astrocytes during astrocytosis.
Nerve growth factor (NGF)
Brain-derived neurotrophic factor (BDNF)
Glial-cell-line-derived neurotrophic factor (GDNF)
Activated microglia express which proteins? What kind of cell does this make them?
MHC Class II
Antigen-presenting cells
