Okadaic acid induces apoptosis in Down syndrome fibroblasts

Topic: Brain proteins, microglia and lab models

Down's syndrome (DS) is characterized by several pathological aspects leading to an increased susceptibility to cardiovascular diseases, infections, leukemia, endocrine alterations. DS patients display some of the physiopathological characteristics of aging, observed also in Alzheimer disease (AD), such as abnormalities in lipids metabolism, diabetes, high cholesterol fraction, senile plaques and neurofibrillary tangles. For this reason DS is considered a precocious and accelerated model of senescence, in which increased apoptosis is the main cornerstone. In order to better understand the apoptotic process in pathological cellular aspects of DS, the aim of this study was to investigate the apoptotic response of DS fibroblasts to OA, a toxin that induces malformations and inhibits growth in different cell lines. We focused specifically on the mitochondrial response by investigating changes in mitochondrial membrane potential (evaluate by flow cytometry and fluorescence microscopy using JC-1 probe) and alterations of mitochondrial outer membrane (evaluated by flow cytometry using annexin V/propidium iodide). Results indicates that DS Fibroblasts have a baseline of apoptosis higher than normal fibroblasts and are more susceptible to the pro-apoptotic effect of OA. Understanding the mechanism of apoptosis in DS fibroblasts could provide new insight in the pathogenic mechanism of this pathology and suggest potential therapeutical targets to the clinical treatment at complex diseases associated to this pathology.

@article{dogliotti2010-20006980,
  author  = {Dogliotti, G. and Galliera, E. and Dozio, E. and Vianello, E. and Villa, R. E. and Licastro, F. and Barajon, I. and Corsi, M. M.},
  title   = {{Okadaic acid induces apoptosis in Down syndrome fibroblasts}},
  journal = {Toxicology in vitro : an international journal published in association with BIBRA},
  year    = {2010},
  doi     = {10.1016/j.tiv.2009.12.012},
  pmid    = {20006980},
  url     = {https://doi.org/10.1016/j.tiv.2009.12.012}
}

Key findings

• Results indicates that DS Fibroblasts have a baseline of apoptosis higher than normal fibroblasts and are more susceptible to the pro-apoptotic effect of OA.

Why it matters

In laboratory studies of skin fibroblasts, cells from people with Down syndrome showed more baseline apoptosis and greater susceptibility to okadaic acid than normal fibroblasts. This is cell-level research and does not establish a treatment or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.tiv.2009.12.012
• PubMed: 20006980
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science (New York, N.Y.) · 1987-02-01 · usefulness score 57/100 · Down syndrome and Alzheimer's
• The pathological association between Down syndrome and Alzheimer disease Mechanisms of ageing and development · 1988-05-01 · usefulness score 44/100 · Down syndrome and Alzheimer's

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• Antioxidants in Down syndrome Biochimica et biophysica acta · 2011-12-21 · usefulness score 39/100 · Down syndrome and Alzheimer's

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• Amyloid of neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence Proceedings of the National Academy of Sciences of the United States of America · 1987-04-01 · usefulness score 39/100
• Amyloid precursor protein-mediated endocytic pathway disruption induces axonal dysfunction and neurodegeneration The Journal of clinical investigation · 2016-04-11 · usefulness score 36/100
• Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL Neurobiology of aging · 2000-07-01 · usefulness score 44/100

Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• Down syndrome postmortem brains exhibit reduction in [ 18 F]nifene binding to α4β2* nicotinic acetylcholinergic receptors bioRxiv · 2026-09-15 · usefulness score 16/100 · Down syndrome and Alzheimer's
• Understanding perspectives and research trends in Down syndrome neuropathogenesis: A bibliometric analysis Journal of intellectual disabilities : JOID · 2024-11-13 · usefulness score 30/100 · Down syndrome and Alzheimer's
• Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome Neuroscience letters · 1999-01-01 · usefulness score 40/100 · Down syndrome and Alzheimer's

Similar studies

• Evidence for apoptosis in the fetal Down syndrome brain 2001 · Down syndrome and Alzheimer's
• Okadaic acid induces early changes in microtubule-associated protein 2 and tau phosphorylation prior to neurodegeneration in cultured cortical neurons 1993 · Biomarkers
• Unaltered expression of Fas (CD95/APO-1), caspase-3, Bcl-2 and annexins in brains of fetal Down syndrome: evidence against increased apoptosis 2001 · Down syndrome and Alzheimer's
• Apolipoprotein A-I: insights from redox proteomics for its role in neurodegeneration 2013 · Down syndrome and Alzheimer's
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• Oxidative stress and Down syndrome. Do antioxidants play a role in therapy? 2014 · Down syndrome and Alzheimer's

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