Improving metabolism prolongs cone cell survival

Retinitis pigmentosa (RP) is an inherited degenerative eye disease that results from the presence of mutations in rod-associated genes. Cone cells, which mediate day light vision, also progressively degrade in RP; however, the mechanisms that mediate loss of these cells are not completely understood. In RP, dying cones exhibit signs of starvation, suggesting metabolic dysfunction in these cells. In this episode, Claudio Punzo and Aditya Venkatesh present their work, which demonstrates that constitutive activation of the metabolic regulator mTORC1 prolongs cone survival and maintains cone function in murine models of RP. The results of this study support further exploration of strategies to improve metabolic function for maintaining cone function in RP.

Insight into hippocampal synaptic plasticity

Synaptic plasticity, or the ability of synapses to strengthen or weaken connections, is thought to underlie learning and memory. In this episode, Erwin Van Meir, Donald Rainnie, and Yoland Smith discuss their work, which identifies brain-specific angiogenesis inhibitor-1 (BAI1) as a determinant of synaptic plasticity and hippocampal-dependent spatial learning and memory in mice. BAI1 prevents degradation the post-synaptic density component PSD-95, and restoration of PSD-95 in the BAI1-deficient hippocampal neurons ameliorated synaptic plasticity deficits.  The results from this study provide insight into pathways that mediate spatial learning and memory, which are altered in several neurological diseases.

Battling cholangiocarcinoma with WNT inhibition

Cholangiocarcinoma is a cancer of the bile duct that has a poor prognosis, largely due to it being refractory to available therapies. In this episode, Stuart Forbes and Luke Bolter reveal that the canonical WNT signaling pathway drives cholangiocarcinoma growth by regulating epithelial cell proliferation. Inflammatory macrophages, which infiltrate the cancer, are a major source of the WNT-inducing signal and thereby facilitate cholangiocarcinoma growth. The results of this study support further investigation into the use of WNT inhibitors to treat cholangiocarcinoma.

James Rothman

In the 1970s and '80s, James Rothman of Yale University bucked all advice on how to do scientific experiments and broke open cells in order to study the way that vesicles are transported. His discovery of the machinery that orchestrates the budding, fusion, and transport of vesicles is key to organelle formation, nutrient uptake, and the secretion of most hormones and neurotransmitters in the body. For this work, Rothman shared the 2013 Nobel Prize in Physiology or Medicine.

Insight into T cell-mediated neuroprotection

Injury to the central nervous system (CNS) results in a cascade of events that leads to cell death and neurodegeneration. Recent studies have shown that T cells infiltrate sites of neuronal injury and are protective against damage, though it is not clear how these cells are activated or mediate neuroprotective effects. In this episode, Jonathan Kipnis, James Walsh, and Frauke Zipp reveal that these beneficial T cell populations are activated by damage-associated signals that originate from damaged CNS tissue. Moreover, these T cells secrete IL-4, which promotes neural survival and regrowth through induction of neurotrophin signaling. The results of this study suggest that strategies to increase IL-4-producing T cells in the CNS have therapeutic potential for limiting neuronal damage as the result of trauma, inflammation, or neurodegeneration.