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PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species.
J Alzheimers Dis. 2009; 17(3):611-9.JA

Abstract

Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.

Authors+Show Affiliations

Panacea Pharmaceuticals, Inc., Gaithersburg, MD 20877, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19433896

Citation

Nelson, Valery M., et al. "PAN-811 Inhibits Oxidative Stress-induced Cell Death of Human Alzheimer's Disease-derived and Age-matched Olfactory Neuroepithelial Cells Via Suppression of Intracellular Reactive Oxygen Species." Journal of Alzheimer's Disease : JAD, vol. 17, no. 3, 2009, pp. 611-9.
Nelson VM, Dancik CM, Pan W, et al. PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. J Alzheimers Dis. 2009;17(3):611-9.
Nelson, V. M., Dancik, C. M., Pan, W., Jiang, Z. G., Lebowitz, M. S., & Ghanbari, H. A. (2009). PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. Journal of Alzheimer's Disease : JAD, 17(3), 611-9. https://doi.org/10.3233/JAD-2009-1078
Nelson VM, et al. PAN-811 Inhibits Oxidative Stress-induced Cell Death of Human Alzheimer's Disease-derived and Age-matched Olfactory Neuroepithelial Cells Via Suppression of Intracellular Reactive Oxygen Species. J Alzheimers Dis. 2009;17(3):611-9. PubMed PMID: 19433896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species. AU - Nelson,Valery M, AU - Dancik,Chantée M, AU - Pan,Weiying, AU - Jiang,Zhi-Gang, AU - Lebowitz,Michael S, AU - Ghanbari,Hossein A, PY - 2009/5/13/entrez PY - 2009/5/13/pubmed PY - 2009/12/16/medline SP - 611 EP - 9 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 17 IS - 3 N2 - Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/19433896/PAN_811_inhibits_oxidative_stress_induced_cell_death_of_human_Alzheimer's_disease_derived_and_age_matched_olfactory_neuroepithelial_cells_via_suppression_of_intracellular_reactive_oxygen_species_ L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=17&issue=3&spage=611 DB - PRIME DP - Unbound Medicine ER -