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Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins involved in intracellular lipid transport and bind free fatty acids, cholesterol, and retinoids. FABP3, the major neuronal FABP in the adult brain, is upregulated in the CSF of patients with Alzheimer's disease (AD). However, the precise role of neuronal FABPs in AD pathogenesis remains unclear. This study investigates the contribution of fabp, the Drosophila homolog of FABP3 and FABP7, to amyloid β (Aβ) pathology using a Drosophila model. Neuronal knockdown of fabp shortened the lifespan of flies and increased age-related protein aggregates in the brain. In an AD model, fabp knockdown in neurons increased Aβ accumulation and Aβ-induced neurodegeneration, whereas fabp overexpression ameliorated Aβ pathology. Notably, fabp overexpression stimulated autophagy, which was inhibited by the knockdown of Eip75B, the Drosophila homolog of the peroxisome proliferator-activated receptor (PPAR). The PPAR activator rosiglitazone restored autophagy impaired by fabp knockdown and reduced fabp knockdown-induced increased Aβ aggregation and cell death. Furthermore, knockdown of either fabp or Eip75B in the wing imaginal disc or adult fly brain reduced the expression of Atg6 and Atg8a. Additionally, treatment of the fabp knockdown AD model flies with polyunsaturated fatty acids, such as docosahexaenoic acid or linoleic acid, partially alleviated cell death in the developing eye, restored impaired autophagy flux, reduced Aβ aggregation, and attenuated Aβ-induced cell death. Our results suggest that Drosophila fabp plays an important role in maintaining protein homeostasis during aging and protects neurons from Aβ-induced cell death by enhancing autophagy through the PPAR pathway. These findings highlight the potential importance of neuronal FABP function in AD pathogenesis. Author summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a gradual progression to severe cognitive impairment and dementia. Despite its high heritability, only a limited number of genes associated with AD have been identified. Understanding the role of disease-associated genes is critical to unraveling the pathology of AD. Given the abnormal protein aggregation seen in AD, genes that affect the degradation of aggregated proteins are expected to be important players. In this study, we focused on FABP, a lipid transport protein that has been observed at elevated levels in the cerebrospinal fluid of patients with AD. The specific role of this protein in neurons affected by AD remained elusive. Using a Drosophila model of AD, we found that reduced expression of fabp in neurons increased accumulation of amyloid β (Aβ) and exacerbated Aβ-induced neurodegeneration. Conversely, overexpression of fabp attenuated these phenotypes. Our results confirm that the protective effect of fabp is mediated through autophagy. In particular, we identified the involvement of the nuclear receptor PPAR in this process. We also demonstrated that neuronal fabp plays a critical role in protein aggregation and lifespan during aging. In conclusion, our study highlights the critical role of neuronal FABP as a regulator in AD pathology and aging. These findings contribute to a better understanding of the molecular mechanisms underlying AD and open avenues for potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

The dermal-epidermal junction (DEJ) provides a physical and biological interface between the epidermis and the dermis. In addition to providing a structural integrity, the DEJ also acts as a passageway for molecular transport. Based on the recently reported importance of the DEJ in skin aging, novel peptide derivatives have been tested for their effects on basement membrane (BM) protein expressions in cultured human epidermal keratinocytes. As a result, protein expressions of collagen XVII, laminin and nidogen were stimulated by the test peptide and peptides complex. Further ex vivo evaluation using excised human skin, confirmed that the topical application of the peptides complex significantly increased dermal collagen expression, as well as expressions of collagen XVII and laminin. Interestingly, while the origin of the laminin protein is epidermal keratinocytes, the immunohistochemical staining of skin showed that laminin was only detected in the uppermost layer of the dermis, which suggests a tight assembly of laminin protein onto the dermal side of the DEJ. These results suggest that a peptide complex could improve the structural properties of the DEJ through its ability to stimulate BM proteins. In order to evaluate the anti-wrinkle benefits of the peptide complex in vivo, a clinical study was performed on 22 healthy Asian female volunteers older than 40 years. As a result, significant improvements in skin wrinkles for all of the five sites were observed after two weeks, as assessed by skin topographic measurements. Collectively, these results demonstrate the anti-aging efficacy of the peptides complex. [ABSTRACT FROM AUTHOR]

Terpenes are vital metabolites found in various plants and animals and known to be beneficial in the treatment of various diseases. Previously, our group identified terpenes that increased the survival of Alzheimer's disease (AD) model flies expressing human amyloid β (A β ) and identified linalool as a neuroprotective terpene against A β toxicity. Linalool is a monoterpene that is commonly present as a constituent in essential oils from aromatic plants and is known to have anti-inflammatory, anticancer, antihyperlipidemia, antibacterial, and neuroprotective properties. Although several studies have shown the beneficial effect of linalool in AD animal models, the mechanisms underlying the beneficial effect of linalool on AD are yet to be elucidated. In the present study, we showed that linalool intake increased the survival of the AD model flies during development in a dose-dependent manner, while the survival of wild-type flies was not affected even at high linalool concentrations. Linalool also decreases A β -induced apoptosis in eye discs as well as the larval brain. Moreover, linalool intake was found to reduce neurodegeneration in the brain of adult AD model flies. However, linalool did not affect the total amount of A β 42 protein or A β 42 aggregation. Rather, linalool decreased A β -induced ROS levels, oxidative stress, and inflammatory response in the brains of AD model flies. Furthermore, linalool attenuated the induction of oxidative stress and gliosis by A β 1-42 treatment in the rat hippocampus. Taken together, our data suggest that linalool exerts its beneficial effects on AD by reducing A β 42-induced oxidative stress and inflammatory reactions., Competing Interests: The authors declare that they have no potential conflicts of interest, including any financial, personal, or other relationships, with other people or organizations., (Copyright © 2021 Chunyu Yuan et al.)