[SIRT1/PGC-1: a neuroprotective axis?].
Neurodegenerative diseases are more and more prevalent in our aging societies. A rapid overview of the etiology of many neurodegenerative diseases like Alzheimer, Parkinson, Huntington disease and amyotrophic lateral sclerosis suggests a tight link with mitochondrial dysfunction. Since it has been recently demonstrated that activation of the SIRT1/PGC-1 pathway, in a metabolic context promotes mitochondrial function, we performed a detailed literature review on the implication of this pathway in neurodegeneration. Interestingly, transgenic mice with impaired PGC-1 expression have neurodegenerative lesions and show behavioural abnormalities. As evidenced from independent investigations, enhanced SIRT1 activity has been demonstrated to protect against axonal degeneration and to decrease the accumulation of amyloid beta peptides, the hallmark of Alzheimer disease, in cultured murine embryonic neurons. In addition, several studies suggest that resveratrol, a specific activator of SIRT1, could have protective effects in animal models of neurodegenerative diseases. Taken together, these results strongly suggest that the modulation of the SIRT1/PGC-1 pathway, which has not been well documented in the central nervous system, could become the cornerstone for new therapeutical approaches to combat neurodegeneration.
Rasouri
Soumya
S
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/Inserm/ULP, 1, rue Laurent Fries, 67404 Illkirch, France.
Lagouge
Marie
M
Auwerx
Johan
J
D000107:Acetylation; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol