Marie-Laure Parmentier

Background Individual, household, and community behaviours influence wider pro-environmental and climate-related outcomes, yet evidence on the outcomes and effectiveness of behaviour change interventions (BCIs) remains fragmented. This umbrella review protocol provides a systematic approach to synthesising accumulated knowledge, identifying general patterns and research gaps in a structured way. Methods This protocol outlines an umbrella review of systematic reviews and meta-analyses (SRMA), following the latest standards for reporting methodological quality, critical appraisal and risk-of-bias assessment. Searches will be conducted across large academic databases in health, behavioural and environmental sciences for records in peer-reviewed journals, published until April 2026. The protocol details a strategy for searching, retrieving, screening, selecting and evaluating records that address BCIs for pro-environmental behaviours among the general population. The selected records will be screened for quality, and the findings will be analysed qualitatively and quantitatively. Data extraction will account for primary studies (covered within reviewed studies), and the synthesis will summarise intervention types, delivery modes, contextual factors, behavioural and mental health outcomes. Expected Results This protocol represents an initial, safeguarding step in the umbrella review process. By following a detailed plan and rigorous standards, the umbrella review is expected to offer reliable insights for policymakers, practitioners, and researchers developing evidence-informed strategies for promoting climate action. Registration In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines ( Shamseer et al., 2015), the following umbrella review protocol was registered via the International Prospective Register of Systematic Reviews (PROSPERO) on 22 October, 2025 (registration number: CRD420251119136).

Tau was initially identified as a microtubule-binding protein critical for microtubule stabilization. It is also a pathological hallmark of tauopathies, a group of neurodegenerative diseases that include Alzheimer’s disease. Under pathological conditions, Tau becomes hyperphosphorylated at numerous sites and aggregates into filamentous deposits, contributing to neuronal cell death and disease progression. While significant research has focused on Tau phosphorylation dynamics and their consequences in pathological contexts, comparatively few studies have investigated Tau phosphorylation during physiological processes, despite the potential relevance to the early onset of pathology. Previous findings have suggested similarities between mitotic Tau phosphorylation and hyperphosphorylation observed in tauopathies, particularly at sites such as AT8, PHF1, S214, and S422. In this study, we quantified the relative levels of phosphorylation at 12 Tau phospho-epitopes during interphase and mitosis in vitro to establish a preliminary mitotic phospho-Tau signature, which was subsequently validated in vivo. Our results demonstrated pronounced phosphorylation of Tau at AT8, p-T217, and p-S422 epitopes during mitosis, both in vitro and in vivo. These findings provide new insights into the physiological phosphorylation of Tau and its potential links to pathological processes.

In addition to the conventional endoplasmic reticulum (ER)‐Golgi secretory pathway, alternative routes are increasingly recognized for their critical roles in exporting a growing number of secreted factors. These alternative processes, collectively referred to as unconventional protein secretion (UcPS), challenge traditional views of protein and membrane trafficking. Unlike the well‐characterized molecular machinery of the conventional secretory pathway, the mechanisms underlying UcPS remain poorly understood. Various UcPS pathways may involve direct transport of cytosolic proteins across the plasma membrane or the incorporation of cargo proteins into intracellular compartments redirected for secretion. Identifying the specific chaperones, transporters and fusion machinery involved in UcPS cargo recognition, selection and transport is crucial to decipher how cargo proteins are selectively or synergistically directed through multiple secretory routes. These processes can vary depending on cell type and in response to particular stress conditions or cellular demands, underscoring the need for standardized tools and methods to study UcPS. Here, we combine the sensitivity of split NanoLuc Binary Technology with the versatility of the Retention Using Selective Hooks (RUSH) system to develop a straightforward and reliable cell‐based assay for investigating both conventional and unconventional protein secretion. This system allows for the identification of intracellular compartments involved in UcPS cargo trafficking. Additionally, its sensitivity enabled us to demonstrate that disease‐associated mutants or variants of Tau and superoxide dismutase‐1 (SOD1) show altered secretion via UcPS. Finally, we leveraged this assay to screen for Alzheimer's disease risk factors, revealing a functional link between amyloid‐beta production and Tau UcPS. This robust assay provides a powerful tool for increasing our knowledge of protein secretion mechanisms in physiological and pathological contexts.

Tau was initially identified as a microtubule-binding protein critical for microtubule stabilization. It is also a pathological hallmark of tauopathies, a group of neurodegenerative diseases that include Alzheimer's disease. Under pathological conditions, Tau becomes hyperphosphorylated at numerous sites and aggregates into filamentous deposits, contributing to neuronal cell death and disease progression. While significant research has focused on Tau phosphorylation dynamics and their consequences in pathological contexts, comparatively few studies have investigated Tau phosphorylation during physiological processes, despite the potential relevance to the early onset of pathology. Previous findings have suggested similarities between mitotic Tau phosphorylation and hyperphosphorylation observed in tauopathies, particularly at sites such as AT8, PHF1, S214, and S422. In this study, we quantified the relative levels of phosphorylation at 12 Tau phospho-epitopes during interphase and mitosis in vitro to establish a preliminary mitotic phospho-Tau signature, which was subsequently validated in vivo. Our results demonstrated pronounced phosphorylation of Tau at AT8, p-T217, and p-S422 epitopes during mitosis, both in vitro and in vivo. These findings provide new insights into the physiological phosphorylation of Tau and its potential links to pathological processes.

In addition to the conventional endoplasmic reticulum (ER)-Golgi secretory pathway, alternative routes are increasingly recognized for their critical roles in exporting a growing number of secreted factors. These alternative processes, collectively referred to as unconventional protein secretion (UcPS), challenge traditional views of protein and membrane trafficking. Unlike the well-characterized molecular machinery of the conventional secretory pathway, the mechanisms underlying UcPS remain poorly understood. Various UcPS pathways may involve direct transport of cytosolic proteins across the plasma membrane or the incorporation of cargo proteins into intracellular compartments redirected for secretion. Identifying the specific chaperones, transporters, and fusion machinery involved in UcPS cargo recognition, selection and transport is crucial to decipher how cargo proteins are selectively or synergistically directed through multiple secretory routes. These processes can vary depending on cell type and in response to particular stress conditions or cellular demands, underscoring the need for standardized tools and methods to study UcPS. Here, we combine the sensitivity of split NanoLuc Binary Technology with the versatility of the Retention Using Selective Hooks (RUSH) system, to develop a straightforward and reliable cell-based assay for investigating both conventional and unconventional protein secretion. This system allows for the identification of intracellular compartments involved in UcPS cargo trafficking. Additionally, its sensitivity enabled us to demonstrate that disease-associated mutants or variants of Tau and superoxide dismutase-1 (SOD1) show altered secretion via UcPS. Finally, we leveraged this assay to screen for Alzheimer's disease risk factors, revealing a functional link between amyloid-beta production and Tau UcPS. This robust assay provides a powerful tool for increasing our knowledge of protein secretion mechanisms in physiological and pathological contexts.

Most secreted proteins are transported through the “conventional” endoplasmic reticulum–Golgi apparatus exocytic route for their delivery to the cell surface and release into the extracellular space. Nonetheless, formative discoveries have underscored the existence of alternative or “unconventional” secretory routes, which play a crucial role in exporting a diverse array of cytosolic proteins outside the cell in response to intrinsic demands, external cues, and environmental changes. In this context, lysosomes emerge as dynamic organelles positioned at the crossroads of multiple intracellular trafficking pathways, endowed with the capacity to fuse with the plasma membrane and recognized for their key role in both conventional and unconventional protein secretion. The recent recognition of lysosomal transport and exocytosis in the unconventional secretion of cargo proteins provides new and promising insights into our understanding of numerous physiological processes.

Eco-anxiety, the anxiety experienced in response to worsening environmental conditions, is a growing worldwide phenomenon. Climate change anxiety is the most commonly recognized form of eco-anxiety, given the escalating impact of ongoing climate change. However, many uncertainties persist regarding the association of this reaction with pro-environmental behaviors as well as its relationship with trait anxiety and perception of the environmental crisis. In this study, we conducted an analysis with a sample size of 431 participants to understand the respective implications of these factors, while considering different levels of intensity in climate anxiety reactions. We measured eco-worry using a short 5-item scale and climate anxiety-related impairments using the Climate Change Anxiety Scale (CCAS). Our findings revealed that eco-worry mediates the relationship between the perception of the environmental crisis and the appearance of climate anxiety-related impairments. Also, eco-worry was found to be constructive in terms of commitment to pro-environmental behaviors, with no additional contribution of the climate anxiety reaction with impairments. Overall, our findings point out the existence of different constructs in the anxiety reaction to climate change and environmental issues, with different factors involved at each level.

Structural microtubule associated protein Tau is found in high amount in axons and is involved in several neurodegenerative diseases. Although many studies have highlighted the toxicity of an excess of Tau in neurons, the in vivo understanding of the endogenous role of Tau in axon morphology and physiology is poor. Indeed, knock-out mice display no strong cytoskeleton or axonal transport phenotype, probably because of some important functional redundancy with other microtubule-associated proteins (MAPs). Here, we took advantage of the model organism Drosophila, which genome contains only one homologue of the Tau/MAP2/MAP4 family to decipher (endogenous) Tau functions. We found that Tau depletion leads to a decrease in microtubule number and microtubule density within axons, while Tau excess leads to the opposite phenotypes. Analysis of vesicular transport in tau mutants showed altered mobility of vesicles, but no change in the total amount of putatively mobile vesicles, whereas both aspects were affected when Tau was overexpressed. In conclusion, we show that loss of Tau in tau mutants not only leads to a decrease in axonal microtubule density, but also impairs axonal vesicular transport, albeit to a lesser extent compared to the effects of an excess of Tau.

Microtubules (MTs) play crucial roles during neuronal life. They are formed by heterodimers of alpha and beta-tubulins, which are subjected to several post-translational modifications (PTMs). Amongst them, glutamylation consists in the reversible addition of a variable number of glutamate residues to the C-terminal tails of tubulins. Glutamylation is the most abundant MT PTM in the mammalian adult brain, suggesting that it plays an important role in the nervous system (NS). Here, we show that the previously uncharacterized CG31108 gene encodes an alpha-tubulin glutamylase acting in the Drosophila NS. We show that this glutamylase, which we named DmTTLL5, initiates MT glutamylation specifically on alpha-tubulin, which are the only glutamylated tubulin in the Drosophila brain. In DmTTLL5 mutants, MT glutamylation was not detected in the NS, allowing for determining its potential function. DmTTLL5 mutants are viable and we did not find any defect in vesicular axonal transport, synapse morphology and larval locomotion. Moreover, DmTTLL5 mutant flies display normal negative geotaxis behavior and their lifespan is not altered. Thus, our work identifies DmTTLL5 as the major enzyme responsible for initiating neuronal MT glutamylation specifically on alpha-tubulin and we show that the absence of MT glutamylation is not detrimental for Drosophila NS function.