Journal Club: Neuroscience, Radiology, Immunology and Cell Biology

Wednesday, November 5, 2014

NEUROSCIENCE: Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons. Berthet, A., et al. (Nakamura). J Neurosci. 2014. 34(43):14304-14317.

Biology textbooks often depict mitochondria, those energy-producing organelles, as little pill-shaped structures scattered throughout the cytoplasm. But mitochondria are highly dynamic structures, fusing and splitting and at times forming large networks.

Recent research suggests that dysregulated mitochondria may play an important role in the development of Parkinson's disease. In this paper, the Nakamura group reports their findings regarding the role of mitochondrial fission in neuron health.

After depleting a protein essential for this mitochondrial fission, they observed a loss of mitochondria, particularly in axons and axon terminals, where signals are sent from one neuron to another. They found that many dopamine neurons, whose disruption is central to Parkinson's disease, were lost. Interestingly, one population of dopamine neurons located in the ventral tegmental area survived despite also showing decreased axonal mitochondria.

RADIOLOGY: A boronate-caged [(18)F]FLT probe for hydrogen peroxide detection using positron emission tomography. Carroll, V., et al. (Chang). J Am Chem Soc. 2014. 136:14742-14745.

Normal metabolism in cells always produces a limited amount of reactive oxygen species (ROS), a category that include hydrogen peroxide and superoxide. Under stressful conditions, the amount of ROS can greatly increase, and scientists are actively investigating the role of ROS in a variety of pathological conditions, such as cancer.

The difficulty of imaging ROS in vivo has been a significant challenge in the field. In this paper, Carroll and colleagues describe the development of a tool for measuring hydrogen peroxide using positron emission tomography (PET), which can be used on whole organisms.

The authors prepared a PET-detectable probe that reacts with hydrogen peroxide. This reaction allows the probe to be taken up and retained by the cell and subsequently detected. Although so far the researchers have only demonstrated the technique successfully using isolated cells, attempts to adopt this technique to in vivo systems are sure to come. 

IMMUNOLOGY: Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Villalta, S.A., et al. (Bluestone). Sci Transl Med. 2014. 6(258):258ra142.

Duchenne muscular dystrophy (DMD) is an incurable, inherited disorder in which progressive muscle degeneration leads to death, usually in early adulthood. DMD is caused by loss-of-function mutations in the dystrophin gene, which is active in muscle cells, but muscle inflammation plays an important role. Indeed, suppression of the immune system has been found to slow disease progression. 

In this paper, the Bluestone group investigated the role of regulatory T cells (T regs), which are immunosuppressive, in a mouse model of DMD. They found T regs in the muscles of these mice; these cells partially restrained muscle inflammation.

They showed that administration of a regulatory T cell-promoting therapy led to increased T regs in the muscles and decreased muscle injury. They speculate that T reg-enhancing agents might be effective DMD therapeutics. 

CELL BIOLOGY: A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Tanenbaum, M.E., et al. (Vale). Cell. 2014. 159(3):635-646.

In biology, less can be more. But sometimes, more is more: easier signal detection, stronger transcription, and so forth.

In this recent article, the authors reported the development of a versatile method for associating a large number of proteins at a single place, and showed two different potential uses. The technology involves a protein scaffold that can be encoded to be a part of any protein. This scaffold can bind up to 24 antibody-fusion proteins, in which a protein of the scientists' choice is joined to the antibody portion.

The authors demonstrated using this scaffold to recruit large numbers of fluorescent proteins, sufficient for the imaging of a single scaffold-tagged protein. They also used the system to recruit large numbers of transcriptional activators, allowing the targeted activation of a particular gene.