The latest medical research on Molecular Genetic Pathology
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about molecular genetic pathology gathered by our medical AI research bot.
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Request AccessAlzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting.
Molecular NeurodegenerationAlzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical in...
Molecular characterization and distribution of motilin and motilin receptor in the Japanese medaka Oryzias latipes.
Cell and Tissue ResearchMotilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vert...
Adaptive immune changes associate with clinical progression of Alzheimer's disease.
Molecular NeurodegenerationAlzheimer's disease (AD) is the most frequent cause of dementia. Recent evidence suggests the involvement of peripheral immune cells in the disease, but the underlying mechanisms remain unclear.
We comprehensively mapped peripheral immune changes in AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF).
We found an adaptive immune signature in AD, and specifically highlight the accumulation of PD1+ CD57+ CD8+ T effector memory cells re-expressing CD45RA in the MCI stage of AD. In addition, several innate and adaptive immune cell subsets correlated to cerebrospinal fluid (CSF) biomarkers of AD neuropathology and measures for cognitive decline. Intriguingly, subsets of memory T and B cells were negatively associated with CSF biomarkers for tau pathology, neurodegeneration and neuroinflammation in AD patients. Lastly, we established the influence of the APOE ε4 allele on peripheral immunity.
Our findings illustrate significant peripheral immune alterations associated with both early and late clinical stages of AD, emphasizing the necessity for further investigation into how these changes influence underlying brain pathology.
Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer's disease.
Molecular NeurodegenerationMicroglia play important roles in maintaining brain homeostasis and neurodegeneration. The discovery of genetic variants in genes predominately or exclusively expressed in myeloid cells, such as Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), as the strongest risk factors for Alzheimer's disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of several microglial proteins are poorly conserved across species, which has hampered the development of strategies aiming to modulate the expression of specific microglial genes. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs).
In this study, we identified, produced, and tested novel, selective and potent ASOs for human APOE and TREM2. We used a combination of in vitro iPSC-microglia models, as well as microglial xenotransplanted mice to provide proof of activity in human microglial in vivo.
We proved their efficacy in human iPSC microglia in vitro, as well as their pharmacological activity in vivo in a xenografted microglia model. We demonstrate ASOs targeting human microglia can modify their transcriptional profile and their response to amyloid-β plaques in vivo in a model of AD.
This study is the first proof-of-concept that human microglial can be modulated using ASOs in a dose-dependent manner to manipulate microglia phenotypes and response to neurodegeneration in vivo.
Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration.
Molecular NeurodegenerationThe unprecedented pandemic of COVID-19 swept millions of lives in a short period, yet its menace continues among its survivors in the form of post-...
Gut microbiota-host lipid crosstalk in Alzheimer's disease: implications for disease progression and therapeutics.
Molecular NeurodegenerationTrillions of intestinal bacteria in the human body undergo dynamic transformations in response to physiological and pathological changes. Alteratio...
Gadolinium retention effect on macrophages - a potential cause of MRI contrast agent Dotarem toxicity.
Cell and Tissue ResearchGadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Do...
Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity.
Molecular NeurodegenerationHypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer's disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain. In this study, we investigated the effects of mitovesicles on synaptic function, and the molecular players involved.
Hippocampal slices from wild-type mice were perfused with the three known types of EVs, mitovesicles, microvesicles, or exosomes, isolated from the brain of a mouse model of Down syndrome or of a diploid control and long-term potentiation (LTP) recorded. The role of the monoamine oxidases type B (MAO-B) and type A (MAO-A) in mitovesicle-driven LTP impairments was addressed by treatment of mitovesicles with the irreversible MAO inhibitors pargyline and clorgiline prior to perfusion of the hippocampal slices.
Mitovesicles from the brain of the Down syndrome model reduced LTP within minutes of mitovesicle addition. Mitovesicles isolated from control brains did not trigger electrophysiological effects, nor did other types of brain EVs (microvesicles and exosomes) from any genotype tested. Depleting mitovesicles of their MAO-B, but not MAO-A, activity eliminated their ability to alter LTP.
Mitovesicle impairment of LTP is a previously undescribed paracrine-like mechanism by which EVs modulate synaptic activity, demonstrating that mitovesicles are active participants in the propagation of cellular and functional homeostatic changes in the context of neurodegenerative disorders.
CD34+ synovial fibroblasts exhibit high osteogenic potential in synovial chondromatosis.
Cell and Tissue ResearchSynovial chondromatosis (SC) is a disorder of the synovium characterized by the formation of osteochondral nodules within the synovium. This study ...
Differential expression of neuropeptide F in the digestive organs of female freshwater prawn, Macrobrachium rosenbergii, during the ovarian cycle.
Cell and Tissue ResearchNeuropeptide F is a key hormone that controls feeding in invertebrates, including decapod crustaceans. We investigated the differential expression ...
The concept of resilience to Alzheimer's Disease: current definitions and cellular and molecular mechanisms.
Molecular NeurodegenerationSome individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer's Disease (AD) neuropathological chan...
Regulatory T cells limit age-associated retinal inflammation and neurodegeneration.
Molecular NeurodegenerationAgeing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.
Regulatory T cells were selectively depleted in both young (2-4 months) and aged (18-23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni's post hoc test.
Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.
Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.
