Peroxisomal proliferation protects from beta-amyloid neurodegeneration.
Alzheimer disease is a neurodegenerative process that leads to severe cognitive impairment as a consequence of selective death of neuronal populations. The molecular pathogenesis of Alzheimer disease involves the participation of the beta-amyloid peptide (Abeta) and oxidative stress. We report here that peroxisomal proliferation attenuated Abeta-dependent toxicity in hippocampal neurons. Pretreatment with Wy-14.463 (Wy), a peroxisome proliferator, prevent the neuronal cell death and neuritic network loss induced by the Abeta peptide. Moreover, the hippocampal neurons treated with this compound, showed an increase in the number of peroxisomes, with a concomitant increase in catalase activity. Additionally, we evaluate the Wy protective effect on beta-catenin levels, production of intracellular reactive oxygen species, cytoplasmic calcium uptake, and mitochondrial potential in hippocampal neurons exposed to H(2) O(2) and Abeta peptide. Results show that the peroxisomal proliferation prevents beta-catenin degradation, reactive oxygen species production, cytoplasmic calcium increase, and changes in mitochondrial viability. Our data suggest, for the first time, a direct link between peroxisomal proliferation and neuroprotection from Abeta-induced degenerative changes.
Santos
Manuel J
MJ
Unidad de Bioquímica Celular y Genética, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
Quintanilla
Rodrigo A
RA
Toro
Andrés
A
Grandy
Rodrigo
R
Dinamarca
Margarita C
MC
Godoy
Juan A
JA
Inestrosa
Nibaldo C
NC
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D047493:PPAR alpha / Q000235:genetics / Q000502:physiology; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D020675:Peroxisomes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D051176:beta Catenin; C006253:pirinixic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D002118:Calcium