The role of Ca2+-stimulated adenylyl cyclases in bidirectional synaptic plasticity and brain function
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Hongbing Wang
und
Ming Zhang
Abstract
The activity-dependent neuronal modification is important for many aspects of adaptive behavior and brain development. Very often, neurological disorders are associated with the alteration of neural signaling pathways that are required for activity-triggered cellular events. Mounting evidence has implicated the role of cyclic AMP (cAMP)-cAMP-dependent protein kinase (PKA)-ERK1/2-cAMP-responsive element-binding protein (CREB) cascade in numerous brain functions such as learning and memory. Ca2+-stimulated type 1 and type 8 adenylyl cyclases (AC1 and AC8) are unique enzymes that couple activity-dependent calcium influx to the activation of cAMP signaling. Here, we summarize some direct evidence to support that Ca2+-stimulated cAMP signaling regulates molecular and cellular substrates of neuronal adaptation. Specifically, the function of AC1 and AC8 in synaptic functions, such as long-term potentiation, long-term depression, and depotentiation, has been examined by using genetic deletion and overexpression approaches. Consistent with the current hypothesis, the Ca2+-stimulated cAMP production through AC1 and AC8 is required for the activity-dependent activation of the ERK1/2-CREB cascade. We further describe the phenotypes of AC1/AC8 mutant mice in memory formation and other adaptive brain functions. The findings may suggest Ca2+-stimulated AC as therapeutic target for the treatment of mental retardation, pain, addiction, anxiety, depression, and neurodegeneration.
©2012 by Walter de Gruyter Berlin Boston
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- GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease
- Mitochondrial and metabolic-based protective strategies in Huntington’s disease: the case of creatine and coenzyme Q
- At a PI3K crossroads: lessons from flies and rodents
- Theta phase precession beyond the hippocampus
- The role of Ca2+-stimulated adenylyl cyclases in bidirectional synaptic plasticity and brain function
- Endoplasmic reticulum stress and prion diseases
- Head models and dynamic causal modeling of subcortical activity using magnetoencephalographic/electroencephalographic data
- The role of glutamatergic inputs onto parvalbumin-positive interneurons: relevance for schizophrenia
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