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Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis. Aloe vera, a miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the Aloe vera flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with Aloe vera flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of Aloe vera flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the Aloe vera flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies. [ABSTRACT FROM AUTHOR]

Introduction: The portfolio of novel targets to treat Alzheimer's disease (AD) has been enriched by the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP AD) program., Methods: Publicly available resources, such as literature and databases, enabled a data-driven effort to identify existing small molecule modulators for many protein products expressed by the genes nominated by AMP AD and suitable positive control compounds to be included in the set. Compounds contained within the set were manually selected and annotated with associated published, predicted, and/or experimental data., Results: We built an annotated set of 171 small molecule modulators targeting 98 unique proteins that have been nominated by AMP AD consortium members as novel targets for the treatment of AD. The majority of compounds included in the set are inhibitors. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which will require further optimization. A physical copy of the AD Informer Set can be requested on the Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) website., Discussion: Small molecules that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD., Competing Interests: Jeffrey Aubé has received compensation from the American Chemical Society, Elsevier Beillstein, Pergament & Cepeda, and the National Institutes of Health as well as consulting fees from the University of Kansas and an honorarium from Case Western Reserve University. He has also served as NIH study section chair twice in the past 36 months and held an unpaid leadership role for the ACS Division of Organic Chemistry. Kevin J. Frankowski received support as a speaker from the Gordon Research Conference. Timothy I. Richardson is an advisor for Enveda Biosciences. Xiaodong Wang received an honorarium and travel support from University of Pittsburgh. Stephen V. Frye received consulting fees from Artios, Astex, GSK‐Crick, Cullgen, Design Therapeutics, Flare, Larkspur, Mitokinin, Pathios, ReViral, Meryx, and eFFector. He has also received honoraria from NIEHS, Scripps, St. Jude, Emory/Winship Cancer Center, Oregon Health Sciences University, University of New Mexico Comprehensive Cancer Center, University of Lexington, and University of Utah. Jessica E. Young received travel reimbursements from AAIC, Columbia University, and Duke University. Jeffrey Aubé, Ivie L. Conlon, Kevin J. Frankowski, Dmitri B. Kireev, Timothy I. Richardson, Xiaodong Wang, Carrow Wells, Timothy M. Willson, Stephen V. Frye, and Alison D. Axtman disclose that they have patents planned, issued, or pending within the past 36 months but that there is no overlap of these patents with the work described herein. All funding provided to the institution and individual authors has been disclosed in the funding information and the declaration of interest section. No other authors have conflict of interests to disclose., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: A chemogenomic set of small molecules with annotated activities and implicated roles in Alzheimer's disease (AD) called the AD Informer Set was recently developed and made available to the AD research community: https://treatad.org/data-tools/ad-informer-set/., Methods: Small subsets of AD Informer Set compounds were selected for AD-relevant profiling. Nine compounds targeting proteins expressed by six AD-implicated genes prioritized for study by Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) teams were selected for G-protein coupled receptor (GPCR), amyloid beta (Aβ) and tau, and pharmacokinetic (PK) studies. Four non-overlapping compounds were analyzed in microglial cytotoxicity and phagocytosis assays., Results: The nine compounds targeting CAPN2, EPHX2, MDK, MerTK/FLT3, or SYK proteins were profiled in 46 to 47 primary GPCR binding assays. Human induced pluripotent stem cell (iPSC)-derived neurons were treated with the same nine compounds and secretion of Aβ peptides (Aβ40 and Aβ42) as well as levels of phosphophorylated tau (p-tau, Thr231) and total tau (t-tau) peptides measured at two concentrations and two timepoints. Finally, CD1 mice were dosed intravenously to determine preliminary PK and/or brain-specific penetrance values for these compounds. As a final cell-based study, a non-overlapping subset of four compounds was selected based on single-concentration screening for analysis of both cytotoxicity and phagocytosis in murine and human microglia cells., Discussion: We have demonstrated the utility of the AD Informer Set in the validation of novel AD hypotheses using biochemical, cellular (primary and immortalized), and in vivo studies. The selectivity for their primary targets versus essential GPCRs in the brain was established for our compounds. Statistical changes in tau, p-tau, Aβ40, and/or Aβ42 and blood-brain barrier penetrance were observed, solidifying the utility of specific compounds for AD. Single-concentration phagocytosis results were validated as predictive of dose-response findings. These studies established workflows, validated assays, and illuminated next steps for protein targets and compounds., Competing Interests: Jeffrey Aubé has received compensation from the American Chemical Society, Elsevier Beillstein, Pergament & Cepeda, and the National Institutes of Health as well as consulting fees from the University of Kansas and an honorarium from Case Western Reserve University. He has also served as NIH study section chair twice in the past 36 months and held an unpaid leadership role for the ACS Division of Organic Chemistry. Kevin J. Frankowski received support as a speaker from the Gordon Research Conference. Timothy I. Richardson is an advisor for Enveda Biosciences and consults with AlphaSights. Xiaodong Wang received an honorarium and travel support from University of Pittsburgh. Stephen V. Frye received consulting fees from Artios, Astex, GSK‐Crick, Cullgen, Design Therapeutics, Flare, Larkspur, Mitokinin, Pathios, ReViral, Meryx, and eFFector. He has also received honoraria from NIEHS, Scripps, St. Jude, Emory/Winship Cancer Center, Oregon Health Sciences University, University of New Mexico Comprehensive Cancer Center, University of Lexington, and University of Utah. Stephen Frye also serves on the UNC CTSA study section as a reviewer. Carrow Wells received funding from the Mark and Chordoma Foundations to support attending meetings and/or travel. Jessica E. Young received travel reimbursements from AAIC, Columbia University, and Duke University. Jeffrey Aubé, Ivie L. Conlon, Kevin J. Frankowski, Dmitri B. Kireev, Timothy I. Richardson, Xiaodong Wang, Carrow Wells, Timothy M. Willson, Stephen V. Frye, and Alison D. Axtman disclose that they have patents planned, issued, or pending within the past 36 months but that there is no overlap of these patents with the work described herein. All funding provided to the institution and individual authors has been disclosed. No other authors have conflicts of interest to disclose., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)