Highlights Neurodegeneration

Neural stem cells (green) in the Telencephalon of an adult Zebrafish.
Neural stem cells (green) in the Telencephalon of an adult Zebrafish.

Repairing Neurons with Light

Using optogenetic methods, researchers have succeeded in stimulating the regeneration processes of neurons. To this end, they used a special form of the enzyme adenylyl cyclase, which is inducible by blue light. The enzyme produces the messenger molecule cAMP, which is required for neuron repair. Because the use of blue light increased the production of cAMP, it became possible by means of the optogenetic system to precisely stimulate the repair of neuronal circuits spatially and temporally.

Yan Xiao et al.: Optogenetic stimulation of neuronal repair. Current Biology  25 (2015) | doi: 10.1016/j.cub.2015.09.038

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Heat Shock Proteins against Amyloids

Heat shock proteins are a promising candidate for the treatment of neurodegenerative diseases. They are able to bind to misfolded proteins and to prevent clumping. For the first time, in the small heat shock protein alpha B-crystallin, those sites were identified by which the protein binds to the beta-amyloid. This is the first direct structural analysis of a complete small heat shock protein in interaction with a binding partner and a prerequisite for the development of drugs.

Andi Mainz et al.: The Chaperone alpha B-Crystallin Deploys Different Interfaces to Capture an Amorphous and an Amyloid Client. Nature Structural Molecular Biology (2015) | doi: 10.1038/nsmb.3108

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Dynamics of Transcription Factors

The results of this study revise existing assumptions about the dynamics and regulation of transcription factors in mouse embryonic stem cells. Scientists of the Institute of Computational Biology conducted an accurate quantification of protein expression over several generations in individual cells. In these the pluripotency protein Nanog is marked with a fluorescent label. While earlier models assigned a central role to Nanog in the regulation machinery, the current study shows that variations in Nanog expression are only associated to a limited extent with differences in the expression of other pluripotent factors.

Adam Filipczyk et al.: Network Plasticity of Pluripotency Transcription Factors in Embryonic Stem Cells. Nature Cell Biology 17 (2015) | doi: 10.1038/ncb3237

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Model to Study HIV Latency in Brain Cells

Over 35 million people worldwide are currently infected by HIV. Although antiviral drugs can contain the infection, they cannot cure it, since the virus hides in a latent, quiescent state in certain cells, among these the astrocytes, brain cells with a very long lifespan. Starting from human neuronal stem cells, the scientists have now established a model for latent HIV infection of brain cells and used this model to investigate the influence of various compounds on the activity of the virus.

Martha Schneider et al.:  A New Model for Post-integration Latency in Macroglial Cells to Study HIV-1 Reservoirs of the Brain. AIDS 29 (2015) | doi:10.1097/QAD.0000000000000691

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Regeneration of Brain Cells

Scientists have succeeded for the first time in directly observing individual neural stem cells in the brain of a living vertebrate by means of live imaging. The observation of processes in the intact and injured brain of zebrafish led to an astonishing finding: Stem cells can convert directly into neurons, whereby the pool of stem cells is depleted. Furthermore, after injury an altered cell division mode increases the yield of neurons.

Joana S. Barbosa et al.: Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.  Science 348 (2015) 789-793 | doi: 10.1126/science.aaa272

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Stem Cells in the Brain: No Eternal Fountain of Youth

Stem cells in the brain can produce neurons and are consequently seen as a hope for the treatment of brain diseases such as dementia. Previously it was believed that the maintenance of the stem cell pool is based on the self-renewal of individual stem cells. Now, however, it has been discovered that the self-renewal rate of stem cells is limited and that their number decreases over the course of a lifetime. New therapeutic approaches shall now focus on the stem cells themselves.

Filippo Calzolari et al.: Fast Clonal Expansion and Limited Neural Stem Cell Self-renewal in the Adult Subependymal Zone. Nature Neuroscience 18 (2015) | doi: 10.1038/nn.3963

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Cellular Transformation in the Brain

Degenerative diseases of the brain such as Alzheimer’s disease or tissue damage in stroke lead to the death of neurons. The cerebral cortex, the brain region responsible for complex thought processes, is not able to replace these cells. Scientists have now discovered in the animal model that glial cells – actually the supporting cells of brain tissue – under certain conditions can convert into neurons in the cerebral cortex – a promising basis for new therapeutic approaches.

Christophe Heinrich et al.: Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex. Stem Cell Reports 3 (2014) | doi: 10.1016/j.stemcr.2014.10.007

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