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Proteinopathies result from aberrant folding and accumulation of specific proteins. Currently, there is a lack of knowledge about the factors that influence disease progression, making this a key challenge for the development of therapies for proteinopathies. Because of the similarities between transmissible spongiform encephalopathies (TSEs) and other protein misfolding diseases, TSEs can be used to understand other proteinopathies. Bovine spongiform encephalopathy (BSE) is a TSE that occurs in cattle and can be subdivided into three strains: classic BSE and atypical BSEs (H and L types) that have shorter incubation periods. The NACHT, LRR, and PYD domainsecontaining protein 3 inflammasome is a critical component of the innate immune system that leads to release of IL-1b. Macroautophagy is an intracellular mechanism that plays an essential role in protein clearance. In this study, the retina was used as a model to investigate the relationship between disease incubation period, prion protein accumulation, neuroinflammation, and changes in macroautophagy. We demonstrate that atypical BSEs present with increased prion protein accumulation, neuroinflammation, and decreased autophagy. This work suggests a relationship between disease time course, neuroinflammation, and the autophagic stress response, and may help identify novel therapeutic biomarkers that can delay or prevent the progression of proteinopathies.

Front Cover: Three‐dimensional microfibrous scaffolds with varying topographies are fabricated using a microfluidic technique to investigate differentiation of neural stem cells. Scaffolds increased proliferation and glial differentiation, showing great potential for biomaterial‐based cell delivery strategies. This is reported by Bhavika B. Patel, Farrokh Sharifi, Daniel P. Stroud, Reza Montazami, Nicole N. Hashemi, Donald S. Sakaguchi in article https://doi.org/10.1002/mabi.201800236.

Background: Bone marrow-derived mesenchymal stem cells (MSCs) have emerged as beneficial cellular vehicles for nervous system rescue and repair. A better understanding how MSCs are involved in mediating neural repair will facilitate development of novel therapeutic strategies. Methods: In the present study bone marrow-derived MSCs were isolated and characterized from Brown Norway rats. The capacity of the MSCs to influence the differentiation of adult hippocampal progenitor cells (AHPCs) was investigated using contact and non-contact co-culture configurations. Results: These MSCs showed a stable and consistent growth rate, retained short population doubling time (PDT) and showed high capacity of cell proliferation. Co-culturing of AHPCs with MSCs did not appear to significantly affect the proliferation of the AHPCs or impact the proportion of neuronal or glial differentiation of the AHPCs. However, both contact co-culture (CCC) and non-contact co-culture (NCCC) significantly promoted neurite outgrowth from neuronal AHPCs. Conclusions: The ability of MSCs to promote the morphological differentiation of AHPCs may serve as an added benefit when developing cell-based strategies for nervous system rescue and repair.

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