This review discusses the driving principles that may underlie neurodegeneration in dementia, represented most dominantly by Alzheimer's disease (AD). While a myriad of different disease risk factors contribute to AD, these ultimately converge to a common disease outcome. Based on decades of research, a picture emerges where upstream risk factors combine in a feedforward pathophysiological cycle, culminating in a rise of cytosolic calcium concentration ([Ca2+]c) that triggers neurodegeneration. In this framework, positive AD risk factors entail conditions, characteristics, or lifestyles that initiate or accelerate self‐reinforcing cycles of pathophysiology, whereas negative risk factors or therapeutic interventions, particularly those mitigating elevated [Ca2+]c, oppose these effects and therefore have neuroprotective potential.

Disruption of the nonhomologous end-joining (NHEJ) pathway has been shown to increase the efficiency of transgene integration into targeted genomic locations of Neurospora crassa and other fungi. Here, we report that a similar phenomenon occurs in a second Neurospora species: N. sitophila. Specifically, we show that deletion of N. sitophila mus-51 increases the efficiency of targeted-transgene integration, presumably by disrupting NHEJ. Researchers interested in obtaining the N. sitophila mus-51 ∆ strains described in this study can obtain them from the

Disruption of the nonhomologous end-joining (NHEJ) pathway has been shown to increase the efficiency of transgene integration into targeted genomic locations of Neurospora crassa and other fungi. Here, we report that a similar phenomenon occurs in a second Neurospora species: N. sitophila. Specifically, we show that deletion of N. sitophila mus-51 increases the efficiency of targeted-transgene integration, presumably by disrupting NHEJ. Researchers interested in obtaining the N. sitophila mus-51 ∆ strains described in this study can obtain them from the Fungal Genetics Stock Center (FGSC).