Neuroscience
Topics of increasing contemporary neuroscientific study are programmed neuron death, the messaging signals for the phenomenon, and potential ways to alter those signals in disease conditions. This review, in the September 2004 issue of Nature Reviews: Neuroscience, provides a detailed look.
Benn SC & Woolf CJ. Adult neuron survival strategies — Slamming on the brakes. Nature Reviews Neuroscience. 2004; 5: 686-700.
Developing neurons are programmed to die by an apoptotic pathway unless they are rescued by extrinsic growth factors that generate an anti-apoptotic response. By contrast, adult neurons need to survive for the lifetime of the organism, and their premature death can cause irreversible functional deficits. The default apoptotic pathway is shut down when development is complete, and consequently growth factors are no longer required to prevent death. To protect against accidental apoptotic cell death, anti-apoptotic mechanisms are activated in mature neurons in response to stress. Loss or reduced activity of these intrinsic anti-apoptotic 'brakes' might contribute to or accelerate neurodegeneration, whereas their activation might rescue neurons from injury or genetic abnormalities.
As the online summary for this review states:
doi:10.1038/nrn1477
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Neuroscience
Today's Reading: Apoptosis
Topics of increasing contemporary neuroscientific study are programmed neuron death, the messaging signals for the phenomenon, and potential ways to alter those signals in disease conditions. This review, in the September 2004 issue of Nature Reviews: Neuroscience, provides a detailed look.
Benn SC & Woolf CJ. Adult neuron survival strategies — Slamming on the brakes. Nature Reviews Neuroscience. 2004; 5: 686-700.
Developing neurons are programmed to die by an apoptotic pathway unless they are rescued by extrinsic growth factors that generate an anti-apoptotic response. By contrast, adult neurons need to survive for the lifetime of the organism, and their premature death can cause irreversible functional deficits. The default apoptotic pathway is shut down when development is complete, and consequently growth factors are no longer required to prevent death. To protect against accidental apoptotic cell death, anti-apoptotic mechanisms are activated in mature neurons in response to stress. Loss or reduced activity of these intrinsic anti-apoptotic 'brakes' might contribute to or accelerate neurodegeneration, whereas their activation might rescue neurons from injury or genetic abnormalities.
As the online summary for this review states:
An anti-apoptotic brake is an intrinsic molecule that can inhibit the apoptotic pathway at one or more points to promote neuronal survival. A cohort of molecules with anti-apoptotic properties or the ability to promote cell survival pathways are induced following acute or chronic neuronal injury, including anti-apoptotic members of the BCL2 family, heat shock proteins, inhibitor of apoptosis proteins, uncoupling proteins and activated protein C.
Apoptotic brakes can be categorized on the basis of their primary site of anti-apoptotic action, as molecules that take effect upstream of mitochondria, at the mitochondrion to prevent the release of cytochrome c and other pro-apoptotic factors, or downstream of mitochondria on effector molecules such as the apoptosome and caspases.
Apoptosis can be suppressed upstream of mitochondria by two main strategies — decoy receptor or ligand proteins, and sequestration or inhibition of pro-apoptotic proteins. Apoptotic brakes that function at the level of the mitochondrion prevent mitochondrial membrane permeabilization and release of apoptotic factors into the cytosol. Downstream of the mitochondria, intrinsic brakes can suppress activation of the executioners of apoptosis, caspases 3, 7 and 9.
An important challenge will be to identify all the anti-apoptotic brakes that are expressed in neurons, along with their mechanisms of action and regulation, and to determine whether induction of specific combinations of anti-apoptotic molecules in selected neuronal populations is beneficial for the treatment of neurological and neurodegenerative diseases.
doi:10.1038/nrn1477
- Neuropsychology Abstract Of The Day: Memory Formation
Visualizing long-term memory formation in two neurons of the Drosophila brain Science. 2012 Feb 10;335(6069):678-85 Chen CC, Wu JK, Lin HW, Pai TP, Fu TF, Wu CL, Tully T, Chiang AS Abstract Long-term memory (LTM) depends on the synthesis of new proteins....
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A press release rom the NIH: Genetic Tags Reveal Secrets of Memories’ Staying Power in Mice A better understanding of how memory works is emerging from a newfound ability to link a learning experience in a mouse to consequent changes in the inner workings...
- Neurodegenerative Diseases: Progranulin (pgrn) Mutation And Tdp-43
From a National Institutes of Health (NIH) press release on the 26th: Scientists Suggest New Pathway Causing Cell Death in Dementia Scientists have discovered a link between a mutated gene and a protein found in dead brain cells of people who suffer...
- Abstract Of The Day: Alzheimer Disease Drug Treatments
Brinton RD & Wang JM (2006). Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res., 3(3), 185-190. Department of Molecular Pharmacology...
- Potassium Channel Regulation Abnormalities In Neurodegeneration
From an NIH press release: Study Implicates Potassium Channel Mutations in Neurodegeneration and Mental Retardation For the first time, researchers have linked mutations in a gene that regulates how potassium enters cells to a neurodegenerative disease...