Search

Background: Participatory architecture can promote dialogue across cultures while working together to create physical outputs. A team of academics with a background in architecture, psychology and health sciences evaluated a participatory architecture workshop in Southern Italy as part of the Crossing Cultures project. The goal was to explore participants' experiences and perceived benefits. In the context of situated learning, the workshop brought together architecture students, local citizens and asylum seekers, who by working together and learning from each other formed a community of practice (CoP). Objective: The aim of this study was to explore the experiences of members of the CoP, their beliefs about the benefits of the project and ways to improve it. Setting: Data collection took place in 2019 during a participatory architecture workshop in Belmonte, Italy. Method: Twenty-five asylum seekers, locals and students took part in in-depth interviews, which were later subjected to thematic analysis. Results: Participants reported experiences relating to 'living together', 'working together', 'making home', 'making locals comfortable to be involved' and 'understanding and respecting differences'. Perceived benefits were 'creating a space for connection', 'revitalising local communities', 'promoting development of towns', 'broadening horizons', 'gaining or practising skills', 'having your ideas heard' and 'creating lasting things'. Conclusion: Findings suggest that creating a CoP not only fulfils individual goals but also addresses common concerns. Participatory architecture workshops in an area with high immigration can create connections between asylum seekers and local people, and promote intercultural dialogue while helping to reactivate an economically and socially deprived area.

Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer's disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis. The results revealed that oxidative phosphorylation and mitochondrial-related pathways are significantly down-regulated in both tissues of Tg2576 mice, supporting the role of these processes in the pathogenesis of AD. In addition, we also analyzed transcriptomic changes occurring in Tg2576 mice treated with the 12A12 monoclonal antibody that neutralizes an AD-relevant tau-derived neurotoxic peptide in vivo . Our analysis showed that the mitochondrial alterations observed in AD mice were significantly reverted by treatment with 12A12mAb, supporting bioenergetic pathways as key mediators of its in vivo neuroprotective and anti-amyloidogenic effects. This study provides, for the first time, a comprehensive characterization of molecular events underlying the disrupted mitochondrial bioenergetics in AD pathology, laying the foundation for the future development of diagnostic and therapeutic tools.

Beyond deficits in hippocampal-dependent episodic memory, Alzheimer's Disease (AD) features sensory impairment in visual cognition consistent with extensive neuropathology in the retina. 12A12 is a monoclonal cleavage specific antibody (mAb) that in vivo selectively neutralizes the AD-relevant, harmful N-terminal 20-22 kDa tau fragment(s) (i.e., NH 2 htau) without affecting the full-length normal protein. When systemically injected into the Tg2576 mouse model overexpressing a mutant form of Amyloid Precursor Protein (APP), APPK670/671L linked to early onset familial AD, this conformation-specific tau mAb successfully reduces the NH 2 htau accumulating both in their brain and retina and, thus, markedly alleviates the phenotype-associated signs. By means of a combined biochemical and metabolic experimental approach, we report that 12A12mAb downregulates the steady state expression levels of APP and Beta-Secretase 1 (BACE-1) and, thus, limits the Amyloid beta (Aβ) production both in the hippocampus and retina from this AD animal model. The local, antibody-mediated anti-amyloidogenic action is paralleled in vivo by coordinated modulation of the endocytic (BIN1, RIN3) and bioenergetic (glycolysis and L-Lactate) pathways. These findings indicate for the first time that similar molecular and metabolic retino-cerebral pathways are modulated in a coordinated fashion in response to 12A12mAb treatment to tackle the neurosensorial Aβ accumulation in AD neurodegeneration.

Tau-targeted immunotherapy is a promising approach for treatment of Alzheimer's disease (AD). Beyond cognitive decline, AD features visual deficits consistent with the manifestation of Amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) in the eyes and higher visual centers, both in animal models and affected subjects. We reported that 12A12-a monoclonal cleavage-specific antibody (mAb) which in vivo neutralizes the neurotoxic, N-terminal 20-22 kDa tau fragment(s)-significantly reduces the retinal accumulation in Tg(HuAPP695Swe)2576 mice of both tau and APP/Aβ pathologies correlated with local inflammation and synaptic deterioration. Here, we report the occurrence of N-terminal tau cleavage in the primary visual cortex (V1 area) and the beneficial effect of 12A12mAb treatment on phenotype-associated visuo-spatial deficits in this AD animal model. We found out that non-invasive administration of 12 A12mAb markedly reduced the pathological accumulation of both truncated tau and Aβ in the V1 area, correlated to significant improvement in visual recognition memory performance along with local increase in two direct readouts of cortical synaptic plasticity, including the dendritic spine density and the expression level of activity-regulated cytoskeleton protein Arc/Arg3.1. Translation of these findings to clinical therapeutic interventions could offer an innovative tau-directed opportunity to delay or halt the visual impairments occurring during AD progression.

The neurosensory retina is an outgrowth of the Central Nervous System (CNS), and the eye is considered "a window to the brain." Reelin glycoprotein is directly involved in neurodevelopment, in synaptic plasticity, learning and memory. Consequently, abnormal Reelin signaling has been associated with brain neurodegeneration but its contributing role in ocular degeneration is still poorly explored. To this aim, experimental procedures were assayed on vitreous or retinas obtained from Reeler mice (knockout for Reelin protein) at different postnatal days (p) p14, p21 and p28. At p28, a significant increase in the expression of Amyloid Precursor Protein (APP) and its amyloidogenic peptide (Aβ1-42 along with truncated tau fragment (i.e., NH 2 htau)- three pathological hallmarks of Alzheimer's disease (AD)-were found in Reeler mice when compared to their age-matched wild-type controls. Likewise, several inflammatory mediators, such as Interleukins, or crucial biomarkers of oxidative stress were also found to be upregulated in Reeler mice by using different techniques such as ELLA assay, microchip array or real-time PCR. Taken together, these findings suggest that a dysfunctional Reelin signaling enables the expression of key pathological features which are classically associated with AD neurodegenerative processes. Thus, this work suggests that Reeler mouse might be a suitable animal model to study not only the pathophysiology of developmental processes but also several neurodegenerative diseases, such as AD and Age-related Macular Degeneration (AMD), characterized by accumulation of APP and/or Aβ1-42, NH 2 htau and inflammatory markers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Balzamino, Esposito, Marino, Calissano, Latina, Amadoro, Keller, Cacciamani and Micera.)