A positive association between insulin resistance and osteoporosis has been widely established. However, crosstalk between the signalling molecules in insulin and Wingless (Wnt)/beta-(β-)catenin transduction cascades orchestrating bone homeostasis remains not well understood. The current review aims to collate the existing evidence, reporting (a) the expression of insulin signalling molecules involved in bone-related disorders and (b) the expression of Wnt/β-catenin signalling molecules involved in governing insulin homeostasis. The downstream effector molecule, glycogen synthase kinase-3 beta (GSK3β), has been identified to be a point of convergence linking the two signal transduction networks. This review highlights that GSK3β may be a drug target in the development of novel anabolic agents and the potential use of GSK3β inhibitors to treat bone-related disorders.
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http://dx.doi.org/10.3390/ijms241512441 | DOI Listing |
Alzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most prevalent cause of dementia accounting for an estimated 60% to 80% of cases. Despite advances in the research field, developing truly effective therapies for AD symptoms remains a major challenge. Sweet almond contain nutrients that have the potential of combating age-related brain dysfunction, by improving learning, memory and neurocognitive performance.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: Human pluripotent stem cell (hPSC)-derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in vivo in cortical tissue. We and others have used these cortical organoids to model dominantly inherited FTD-tau. While these studies have provided essential insights, cortical organoid models have yet to reach their full potential.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
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