Abstract
BAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria. Here we evaluate the function of BAK in several mouse models of neuronal injury including neuronotropic Sindbis virus infection, Parkinson's disease, ischemia/stroke, and seizure. BAK promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. BAK protects neurons from excitotoxicity and virus infection in the hippocampus. As mice mature, BAK is converted from anti- to pro-death function in virus-infected spinal cord neurons. In addition to regulating cell death, BAK also protects mice from kainate-induced seizures, suggesting a possible role in regulating synaptic activity. BAK can alter neurotransmitter release in a direction consistent with its protective effects on neurons and mice. These findings suggest that BAK inhibits cell death by modifying neuronal excitability.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Age Factors
-
Animals
-
Animals, Newborn
-
Apoptosis / genetics*
-
Central Nervous System / metabolism*
-
Central Nervous System / physiopathology
-
Central Nervous System / virology
-
Central Nervous System Diseases / genetics
-
Central Nervous System Diseases / metabolism*
-
Central Nervous System Viral Diseases / genetics
-
Central Nervous System Viral Diseases / metabolism
-
Disease Models, Animal
-
Epilepsy / genetics
-
Epilepsy / metabolism
-
Excitatory Postsynaptic Potentials / drug effects
-
Excitatory Postsynaptic Potentials / genetics
-
Genetic Vectors / genetics
-
Hippocampus / metabolism
-
Hippocampus / physiopathology
-
Hippocampus / virology
-
Kainic Acid
-
Male
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Mice, Knockout
-
Neurodegenerative Diseases / genetics
-
Neurodegenerative Diseases / metabolism
-
Neurons / metabolism*
-
Neurons / pathology
-
Neurons / virology
-
Neurotoxins / genetics
-
Neurotoxins / metabolism
-
Protein Structure, Tertiary / genetics
-
Sindbis Virus / genetics
-
Stroke / genetics
-
Stroke / metabolism
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / genetics*
-
bcl-2 Homologous Antagonist-Killer Protein
Substances
-
Bak1 protein, mouse
-
Membrane Proteins
-
Neurotoxins
-
bcl-2 Homologous Antagonist-Killer Protein
-
Kainic Acid