Therapeutics for mitochondrial dysfunction-linked diseases in Down syndrome

Topic: Brain proteins, microglia and lab models

Genome-wide deregulation contributes to mitochondrial dysfunction and impairment in oxidative phosphorylation (OXPHOS) mechanism resulting in oxidative stress, increased production of reactive oxygen species (ROS) and cell death in individuals with Down syndrome (DS). The cells, which require more energy, such as muscles, brain and heart are greatly affected. Impairment in mitochondrial network has a direct link with patho-mechanism at cellular and systemic levels at the backdrop of generalized metabolic perturbations in individuals with DS. Myriads of clinico-phenotypic features, including intellectual disability, early aging and neurodegeneration, and Alzheimer disease (AD)-related dementia are inevitable in DS-population where mitochondrial dysfunctions play the central role. Collectively, the mitochondrial abnormalities and altered energy metabolism perturbs several signaling pathways, particularly related to neurogenesis, which are directly associated with cognitive development and early onset of AD in individuals with DS. Therefore, therapeutic challenges for amelioration of the mitochondrial defects were perceived to improve the quality of life of the DS population. A number of pharmacologically active natural compounds such as polyphenols, antioxidants and flavonoids have shown convincing outcome for reversal of the dysfunctional mitochondrial network and oxidative metabolism, and improvement in intellectual skill in mouse models of DS and humans with DS.

Key findings

• Collectively, the mitochondrial abnormalities and altered energy metabolism perturbs several signaling pathways, particularly related to neurogenesis, which are directly associated with cognitive development and early onset of AD in individuals with DS.

Why it matters

This review discusses how mitochondrial dysfunction and oxidative stress in Down syndrome may contribute to cognitive problems and early Alzheimer's disease, and mentions natural compounds such as polyphenols, antioxidants and flavonoids as showing promising results. It reports no confirmed treatment, cure or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.mito.2022.11.003
• PubMed: 36371073
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{ganguly2023-36371073,
  author  = {Ganguly, B. B. and Kadam, N. N.},
  title   = {{Therapeutics for mitochondrial dysfunction-linked diseases in Down syndrome}},
  journal = {Mitochondrion},
  year    = {2023},
  doi     = {10.1016/j.mito.2022.11.003},
  pmid    = {36371073},
  url     = {https://doi.org/10.1016/j.mito.2022.11.003}
}

Studies this one cites

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

• The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies Proceedings of the National Academy of Sciences of the United States of America · 2009-07-13 · usefulness score 57/100 · Down syndrome and Alzheimer's
• Down syndrome Nature reviews. Disease primers · 2020-02-06 · usefulness score 56/100 · How common it is
• Down syndrome and the complexity of genome dosage imbalance Nature reviews. Genetics · 2016-12-28 · usefulness score 51/100 · Down syndrome and Alzheimer's
• The effect of acetyl-L-carnitine administration on persons with Down syndrome Research in developmental disabilities · 2006-04-18 · usefulness score 49/100 · Down syndrome and Alzheimer's
• Association between frontal cortex oxidative damage and beta-amyloid as a function of age in Down syndrome Biochimica et biophysica acta · 2011-10-08 · usefulness score 47/100 · Down syndrome and Alzheimer's
• Intrinsic defect of the immune system in children with Down syndrome: a review Clinical and experimental immunology · 2009-01-22 · usefulness score 41/100 · Down syndrome and Alzheimer's
• Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation Neurobiology of aging · 2011-05-23 · usefulness score 39/100 · Down syndrome and Alzheimer's
• Antioxidants in Down syndrome Biochimica et biophysica acta · 2011-12-21 · usefulness score 39/100 · Down syndrome and Alzheimer's

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions Antioxidants (Basel, Switzerland) · 2026-04-21 · usefulness score 39/100 · Down syndrome and Alzheimer's
• Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging? Aging and disease · 2025-04-06 · usefulness score 36/100 · Down syndrome and Alzheimer's
• The many "Neurofaces" of Prohibitins 1 and 2: Crucial for the healthy brain, dysregulated in numerous brain disorders Journal of chemical neuroanatomy · 2023-07-29 · usefulness score 35/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• Oxidative stress and mitochondrial dysfunction in Down syndrome Advances in experimental medicine and biology · 2012-01-01 · usefulness score 41/100
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• Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and down syndrome dementia Journal of Alzheimer's disease : JAD · 2010-01-01 · usefulness score 36/100
• Mitochondrial Dysfunction, Oxidative Stress, and Neuroinflammation: Intertwined Roads to Neurodegeneration Antioxidants (Basel, Switzerland) · 2020-07-22 · usefulness score 41/100
• Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases Neurobiology of aging · 2005-03-01 · usefulness score 36/100
• The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene Nature · 1987-09-01 · usefulness score 41/100

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