c-Jun N-terminal kinases (JNKs) are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death, and regulation of cellular senescence. It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or Aβ peptides. Altogether, JNKs have become a focus of screening strategies searching for new therapeutic approaches to diabetes, cancer or liver diseases. In addition, activation of JNK has been identified as a key element responsible for the regulation of apoptosis signals and therefore, it is critical for pathological cell death associated with neurodegenerative diseases and, among them, with Alzheimer’s disease (AD). In addition, in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with pathogenesis and neuronal death in AD. JNK’s, particularly JNK3, not only enhance Aβ production, moreover it plays a key role in the maturation and development of neurofibrillary tangles. This review aims to explain the rationale behind testing therapies based on inhibition of JNK signaling for AD in terms of current knowledge about the pathophysiology of the disease. Keeping in mind that JNK3 is specifically expressed in the brain and activated by stress-stimuli, it is possible to hypothesize that inhibition of JNK3 might be considered as a potential target for treating neurodegenerative mechanisms associated with AD.

c-Jun N-terminal kinase 3 (JNK3) is suggested to play a key role in neurodegenerative disorders, especially in Alzheimer’s disease (AD). However, it remains unclear whether JNK or amyloid β (Aβ) appears first in the disease onset. Postmortem brain tissues from four dementia subtypes of patients (frontotemporal dementia, Lewy body dementia, vascular dementia, and AD) were used to measure activated JNK (pJNK) and Aβ levels. pJNK expression is significantly increased in AD; however, similar pJNK expression was found in other dementias. Furthermore, there was a significant correlation, co-localization, and direct interaction between pJNK expression and Aβ levels in AD. Significant increased levels of pJNK were also found in Tg2576 mice, a model of AD. In this line, Aβ42 intracerebroventricular injection in wild-type mice was able to induce a significant elevation of pJNK levels. JNK3 overexpression, achieved by intrahippocampal injection of an adeno-associated viral vector expressing this protein, was enough to induce cognitive deficiencies and precipitate Tau aberrant misfolding in Tg2576 mice without accelerating amyloid pathology. JNK3 overexpression may therefore be triggered by increased Aβ. The latter, together with subsequent involvement of Tau pathology, may be underlying cognitive alterations in early stages of AD.

A potential role of marine n-3 polyunsaturated fatty acids (ω-3 PUFAs) has been suggested in memory, learning, and cognitive processes. Therefore, ω-3 PUFAs might be a promising treatment option, albeit controversial, for Alzheimer's disease (AD). Among the different mechanisms that have been proposed as responsible for the beneficial effects of ω-3 PUFAs, inhibition of JNK stands as a particularly interesting candidate. In the present work, it has been studied whether the administration of two different PUFAs (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) and a DHA-derived specialized pro-resolving lipid mediator (MaR1) is able to reverse cognitive deficits in the senescence-accelerated mouse prone 8 (SAMP8) mouse model of sporadic AD. The novel object recognition test (NORT) test showed that recognition memory was significantly impaired in SAMP8 mice, as shown by a significantly decreased discrimination index that was reversed by MaR1 and DHA. In the retention phase of the Morris water maze (MWM) task, SAMP8 mice showed memory deficit that only DHA treatment was able to reverse. pJNK levels were significantly increased in the hippocampus of SAMP8 mice compared to SAMR1 mice, and only DHA treatment was able to significantly reverse these increased pJNK levels. Similar results were found when measuring c-Jun, the main JNK substrate. Consequently to the increases in tau phosphorylation after increased pJNK, it was checked that tau phosphorylation (PHF-1) was increased in SAMP mice, and this effect was reversed after DHA treatment. Altogether, DHA could represent a new approach for the treatment of AD through JNK inhibition.

In this study, the possibility of applying the Life Cycle Thinking approach to structural design, considering all aspects and phases of the structure’s life, is investigated. The idea is to develop a procedure for the analysis of the economic and environmental impacts of structures in their life cycle, including not only ordinary costs along life cycle phases but also the extraordinary costs resulting from damage and anticipated end-of-life caused by unexpected natural hazards. The building performance under extraordinary conditions is calculated according to a time-based Loss Assessment Analysis. Such analysis provides the probable performance of a building and its components over a given period of time, considering all the hazardous events that can occur in that period, the probability of occurrence of each event, and the related effects. The outlined approach is applied to a case study of a single-story steel office building located in Italy. Two LC scenarios, having a duration of 2 years and 50 years, are considered. Results show that contributions of environmental impacts and benefits related to end-of-life management and economic losses for natural hazards are significant and not negligible. It is highlighted that the greatest challenge faced when using such a comprehensive approach is represented by data availability and representativeness that deeply limits the possibility of its implementation.

The existence of chromatic aberrations such as leucism or albinism is the result of inbreeding in isolated populations of wild local fauna and is associated with environmental stressors. This anomaly may reduce survival rates. There are many cases of leucism in wildlife, but overall, it is considered very rare. In neotropical primates, there have been records of leucism but previously, in howler monkeys was unknown. In this article, we report for the first time leucistic young individuals of Mantled howler monkeys Alouatta palliata, subspecies A. p. aequatorialis in an isolated remanent of tropical dry forest in southwestern Ecuador, namely Cerro Blanco Protective Forest. In total, we found two individuals, we named them Albita (a female) and Japu (a male). We also include a spatial analysis of the covert forest loss between 2000 to 2020. The report of individuals with leucism, may imply inbreeding because of isolated populations. Thus, immediate management strategies must be considered to significantly increase connectivity with other populations of howler monkeys.