Abstract
Aging has been a subject of interest since primordial times. More recently, it became clear that aging is the major known risk factor for several neurodegenerative disorders, such as Alzheimers disease, Parkinsons disease and Huntingtons disease. A major focus in the field of aging is to examine whether the genetic regulators of lifespan also regulate the trigger and/or progression of age-related disorders. Sirtuins, which belong to the Sir2 family of NAD+-dependent deacetylases, are known to regulate longevity in yeast, worms, and flies. In mammals, there are seven homologs of the yeast Sir2, Sirt1-7. Therefore, the challenge now is to unravel howthe seven mammalian Sir2 proteins communicate to regulate the cross talk between aging and the onset and progression of age-related disorders. Here, we review how sirtuins contribute for aging and, in particular, for neurodegeneration and how they are becoming attractive targets for therapeutic intervention.
Keywords: Neurodegeneration, sirtuins, Parkinson's disease, Alzheimer's disease, therapeutic targets, aging, Sir2 family, NAD+, O-acetyle ADP ribose, Caloric restriction, Inflammatory diseases, Oxidative stress, Protein misfolding, Mitochondrial dysfunction, Huntington's disease, Sir complex, Heterochromatin, rDNA array, C. elegans, Reservatrol, Drosophila, Apoptosis, p53, Ku70, Forkhead transcription factors, CR trials, PGC-1α, Replication, Transcription, Hsf-1, Heat shock proteins, CAG-repeats, PolyQ, Substantia nigra, Lewy bodies, α-synuclein, OHDA, MPTP, High-throughput screenings, Fluorescent biochemical assays, 1,4-dihydropyridine-based derivatives, 2-anilinobenzamide, Carbomido-NAD+, Sirtinol, Kinase inhibitors
Current Drug Targets
Title: Sirtuins: Common Targets in Aging and in Neurodegeneration
Volume: 11 Issue: 10
Author(s): Rita Machado de Oliveira, Teresa F. Pais and Tiago Fleming Outeiro
Affiliation:
Keywords: Neurodegeneration, sirtuins, Parkinson's disease, Alzheimer's disease, therapeutic targets, aging, Sir2 family, NAD+, O-acetyle ADP ribose, Caloric restriction, Inflammatory diseases, Oxidative stress, Protein misfolding, Mitochondrial dysfunction, Huntington's disease, Sir complex, Heterochromatin, rDNA array, C. elegans, Reservatrol, Drosophila, Apoptosis, p53, Ku70, Forkhead transcription factors, CR trials, PGC-1α, Replication, Transcription, Hsf-1, Heat shock proteins, CAG-repeats, PolyQ, Substantia nigra, Lewy bodies, α-synuclein, OHDA, MPTP, High-throughput screenings, Fluorescent biochemical assays, 1,4-dihydropyridine-based derivatives, 2-anilinobenzamide, Carbomido-NAD+, Sirtinol, Kinase inhibitors
Abstract: Aging has been a subject of interest since primordial times. More recently, it became clear that aging is the major known risk factor for several neurodegenerative disorders, such as Alzheimers disease, Parkinsons disease and Huntingtons disease. A major focus in the field of aging is to examine whether the genetic regulators of lifespan also regulate the trigger and/or progression of age-related disorders. Sirtuins, which belong to the Sir2 family of NAD+-dependent deacetylases, are known to regulate longevity in yeast, worms, and flies. In mammals, there are seven homologs of the yeast Sir2, Sirt1-7. Therefore, the challenge now is to unravel howthe seven mammalian Sir2 proteins communicate to regulate the cross talk between aging and the onset and progression of age-related disorders. Here, we review how sirtuins contribute for aging and, in particular, for neurodegeneration and how they are becoming attractive targets for therapeutic intervention.
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Cite this article as:
Machado de Oliveira Rita, F. Pais Teresa and Fleming Outeiro Tiago, Sirtuins: Common Targets in Aging and in Neurodegeneration, Current Drug Targets 2010; 11 (10) . https://dx.doi.org/10.2174/1389450111007011270
DOI https://dx.doi.org/10.2174/1389450111007011270 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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