Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia globally. No reliable diagnostic, predictive techniques, or curative interventions are ...available. MicroRNAs (miRNAs) are vital to controlling gene expression, making them valuable biomarkers for diagnosis and prognosis. This study examines the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs) derived from individuals with the PSEN1(A431E) mutation (Jalisco mutation). The aim is to determine whether this mutation affects the transcriptome and expression profile of miRNAs and their target genes at different stages of asymptomatic, presymptomatic, and symptomatic conditions. Expression microarrays compare the MSCs from mutation carriers with those from healthy donors. The results indicate a distinct variation in the expression of miRNAs and mRNAs among different symptomatologic groups and between individuals with the mutation. Using bioinformatics tools allows us to identify target genes for miRNAs, which in turn affect various biological processes and pathways. These include the cell cycle, senescence, transcription, and pathways involved in regulating the pluripotency of stem cells. These processes are closely linked to inter- and intracellular communication, vital for cellular functioning. These findings can enhance our comprehension and monitoring of the disease's physiological processes, identify new disorder indicators, and develop innovative treatments and diagnostic tools for preventing or treating AD.
Endophytes, microorganisms that live in the internal tissues and organs of the plants, are known to produce numerous bioactive compounds, including, at times, some phytochemicals of their host plant. ...For such reason, endophytes have been quoted as a potential source for discovering bioactive compounds, particularly, of medical interest. Currently, many non-communicable diseases are threatening global human health, noticeably: diabetes, neurodegenerative diseases, cancer, and other ailment related to chronic inflammation and ageing. Intriguingly, the pathogenesis and development of these diseases have been linked to an excessive formation and accumulation of advanced glycation end products (AGEs). AGEs are a heterogeneous group of compounds that can alter the conformation, function, and lifetime of proteins. Therefore, compounds that prevent the formation and consequent accumulation of AGEs (AntiAGEs compounds) could be useful to delay the progress of some chronic diseases, and/or harmful effects of undue AGEs accumulation. Despite the remarkable ability of endophytes to produce bioactive compounds, most of the natural antiAGEs compounds reported in the literature are derived from plants. Accordingly, this work covers 26 plant antiAGEs compounds and some derivatives that have been reported as endophytic metabolites, and discusses the importance, possible advantages, and challenges of using endophytes as a potential source of antiAGEs compounds.
Alzheimer’s disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully ...understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer’s Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.
Mesenchymal stem cells (MSCs) are self-renewing cells found in almost all postnatal organs and tissues in the perivascular region. These cells have a high capacity for mesodermal differentiation; ...however, numerous studies have shown that MSCs can also differentiate into cells of endodermal and ectodermal lineages. Due to this multilineage differentiation capacity, these cells could function as restoratives of various cell populations after transplantation. However, not only their differentiation potential makes them ideal candidates for this, but also a series of trophic properties that promote regeneration in the surrounding tissue, such as their migratory capacity, secretory and immunomodulatory actions. This review analyzes several MSC transplantation trials to treat neurological diseases, such as demyelinating injury, spinal cord injury, paraplegia, Parkinson's disease, cochlear injury, and Alzheimer's disease. These cells could facilitate functional recovery in multiple models of neurodegenerative diseases and nervous system injuries by using their trophic capacities, reducing inflammation in the injured area, reducing apoptosis, and enhancing endogenous neurogenesis through the secretion of bioactive factors. Furthermore, since cells derived from patients have demonstrated disease-associated differences in various brain diseases, these cells represent an excellent candidate for the study of these diseases, functioning as "a window to the brain."