The Child Is Father to the Man: Developmental Roles for Proteins of Importance for Neurodegenerative Disease

University of Rochester, Rochester, New York, United States
Annals of Neurology (Impact Factor: 11.91). 02/2010; 67(2):151-8. DOI: 10.1002/ana.21841
Source: PubMed

ABSTRACT Although Alzheimer's and Parkinson's diseases predominately affect elderly adults, the proteins that play a role in the pathogenesis of these diseases are expressed throughout life. In fact, many of the proteins hypothesized to be important in the progression of neurodegeneration play direct or indirect roles in the development of the central nervous system. The systems affected by these proteins include neural stem cell fate decisions, neuronal differentiation, cellular migration, protection from oxidative stress, and programmed cell death. Insights into the developmental roles of these proteins may ultimately impact the understanding of neurodegenerative diseases and lead to the discovery of novel treatments.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Alterations in embryonic neural stem cells play crucial roles in the pathogenesis of amyotrophic lateral sclerosis. We hypothesized that embryonic neural stem cells from SOD1(G93A) individuals might be more susceptible to oxidative injury, resulting in a propensity for neurodegeneration at later stages. In this study, embryonic neural stem cells obtained from human superoxide dismutase 1 mutant (SOD1(G93A)) and wild-type (SOD1(WT)) mouse models were exposed to H2O2. We assayed cell viability with mitochondrial succinic dehydrogenase colorimetric reagent, and measured cell apoptosis by flow cytometry. Moreover, we evaluated the expression of the adenosine monophosphate-activated protein kinase (AMPK) α-subunit, paired box 3 (Pax3) protein, and p53 in western blot analyses. Compared with SOD1(WT) cells, SOD1(G93A) embryonic neural stem cells were more likely to undergo H2O2-induced apoptosis. Phosphorylation of AMPKα in SOD1(G93A) cells was higher than that in SOD1(WT) cells. Pax3 expression was inversely correlated with the phosphorylation levels of AMPKα. p53 protein levels were also correlated with AMPKα phosphorylation levels. Compound C, an inhibitor of AMPKα, attenuated the effects of H2O2. These results suggest that embryonic neural stem cells from SOD1(G93A) mice are more susceptible to apoptosis in the presence of oxidative stress compared with those from wild-type controls, and the effects are mainly mediated by Pax3 and p53 in the AMPKα pathway.
    Neural Regeneration Research 10/2014; 9(19):1770-1778. DOI:10.4103/1673-5374.143421 · 0.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma is, at once, the most common and deadly extracranial solid tumor of childhood. Efforts aimed at targeting the neural characteristics of these tumors have taught us much about neural crest cell biology, apoptosis induction in the nervous system, and neurotrophin receptor signaling and intracellular processing. But neuroblastoma remains a formidable enemy to the oncologist and an enigmatic target to the neuroscientist.
    Journal of child neurology 04/2013; 28(6). DOI:10.1177/0883073813483173 · 1.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The increasing longevity of patients with congenital and developmental disorders of the nervous system reflects the palliative and social success of pediatrics in the past two decades. This success has resulted in an increasing number of adult patients with residua or sequelae of childhood disease and/or its treatment. It is critically important that residencies and subspecialty fellowships train a cadre of physicians to prepare patients and families for the transition of children with special health care needs to adulthood and to attend to their unique medical, psychological, and social concerns. Health services and education research must better define the needs of this growing population and the best ways to educate their physicians and families and empower them to become as independent as their fullest potential allows. ANN NEUROL 2013. © 2013 American Neurological Association.
    Annals of Neurology 04/2013; 74(2). DOI:10.1002/ana.23910 · 11.91 Impact Factor