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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens zachary fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

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Boldness and predator evasion in naturally hybridizing swordtails （Teleostei： Xiphophorus）

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Current Zoology 2015年第4期61卷 596-603页

作者： James B. JOHNSON zachary W. CULUMBER Ryan EASTERLING Gil G. R.OSENTHAL Department of Biology Texas A&M University College Station Texas TX 77843 USA Centro de lnvestigaciones Cientificas de las Huastecas "Aguazarca" Calnali Hidalgo Mexico

Correlations among behavioral traits can generate trade-offs and constrain phenotypic evolution. Interspecific hybridization has the potential to alter behavioral trait correlations, but the effect of hybridization on suites of behavioral traits has received relatively little attention. We evaluated how natural hybridization changes the relationship between boldness （time of emergence and proportion of time out of shelter） and response to a simulated predator threat in swordtails （Teleostei： Xiphophorus）. In poeciliid fishes, bold individuals have increased survival in the presence of predators. This non-intuitive observation may arise as a result of bold individuals being more likely to engage in anti-predator behaviors. Contrary to our prediction, bold indi- viduals were less likely to perform a fast-start response to a predator threat. This correlation was consistent among populations and species but was only significant in hybrids. The observed correlation between boldness and anti-predator behavior could im- pact hybrid fitness and the evolvability of hybrid lineages. More generally, our findings suggest that hybridization could influence the integration of behavioral phenotypes, as has been amply documented for morphology. Animal personality and behavioral syndromes could therefore play an important role in the evolutionary fate of natural hybrids [Current Zoology 61 （4）： 596-603, 2015].

关键词： Trait compensation Fast-Start Anti-predator behavior hybridization Behavioral syndrome Animal personality

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