Abstract
Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the “acetylome.” At present, it is estimated that acetylome covers only one tenth of the proteome, however, due its potential significance in physiology is capturing great attention. The first components of the cellular machinery, which finely orchestrate acetylome homeostasis, were identified by the end of last century. Since then, the majority of our growing knowledge concerning the physiological relevance of proteome reversible acetylation comes from the study of sirtuins, a unique type of lysine deacetylase that uses NAD+. Sirtuins participate in a variety of cellular processes, ranging from transcription, DNA repair, energy balance, mitochondrial biogenesis and cell division, to apoptosis, autophagy and aging. Within the brain, besides their widespread epigenetic effects of dynamically modifying histones, sirtuins also target a variety of non-histone proteins either commonly deregulated in pathologies, or that participate in normal cerebral functions. For example, they modulate critical elements of the circadian rhythms, neurogenesis, synapses, cognition, serotonin synthesis, myelination, and proteins involved in neuropathology. Acetylome dynamics, and its regulation by sirtuins, may also help to better understand the molecular mechanisms underlying brain aging. This work reviews the pathways as orchestrated by the interplay between acetylome and sirtuins in the brain, from physiology involvement, to aging processes, and pathological settings.
Keywords: Acetylome, sirtuins, aging, neurodegeneration, SIRT1, reversible lysine acetylation, brain, lysine acetyltransferases, lysine deacetylases, calorie restriction
Current Pharmaceutical Design
Title:Acetylome Regulation by Sirtuins in the Brain: From Normal Physiology to Aging and Pathology
Volume: 19 Issue: 38
Author(s): Shaday Michan
Affiliation:
Keywords: Acetylome, sirtuins, aging, neurodegeneration, SIRT1, reversible lysine acetylation, brain, lysine acetyltransferases, lysine deacetylases, calorie restriction
Abstract: Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the “acetylome.” At present, it is estimated that acetylome covers only one tenth of the proteome, however, due its potential significance in physiology is capturing great attention. The first components of the cellular machinery, which finely orchestrate acetylome homeostasis, were identified by the end of last century. Since then, the majority of our growing knowledge concerning the physiological relevance of proteome reversible acetylation comes from the study of sirtuins, a unique type of lysine deacetylase that uses NAD+. Sirtuins participate in a variety of cellular processes, ranging from transcription, DNA repair, energy balance, mitochondrial biogenesis and cell division, to apoptosis, autophagy and aging. Within the brain, besides their widespread epigenetic effects of dynamically modifying histones, sirtuins also target a variety of non-histone proteins either commonly deregulated in pathologies, or that participate in normal cerebral functions. For example, they modulate critical elements of the circadian rhythms, neurogenesis, synapses, cognition, serotonin synthesis, myelination, and proteins involved in neuropathology. Acetylome dynamics, and its regulation by sirtuins, may also help to better understand the molecular mechanisms underlying brain aging. This work reviews the pathways as orchestrated by the interplay between acetylome and sirtuins in the brain, from physiology involvement, to aging processes, and pathological settings.
Export Options
About this article
Cite this article as:
Michan Shaday, Acetylome Regulation by Sirtuins in the Brain: From Normal Physiology to Aging and Pathology, Current Pharmaceutical Design 2013; 19 (38) . https://dx.doi.org/10.2174/1381612811319380014
DOI https://dx.doi.org/10.2174/1381612811319380014 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Role of the heme oxygenase-adiponectin-atrial natriuretic peptide axis in renal function
Current Pharmaceutical Design GRK2 Inhibition in Heart Failure: Something Old, Something New
Current Pharmaceutical Design Stage A: Can Heart Failure Be Prevented?
Current Cardiology Reviews Targeting Mitochondria for Cardiac Protection
Current Drug Targets Protein-mediated Fatty Acid Uptake in the Heart
Current Cardiology Reviews Effects of Tea Catechins on Inflammation-Related Cardiovascular Diseases
Current Immunology Reviews (Discontinued) Recent Studies on Neural Tube Defects in Embryos of Diabetic Pregnancy: An Overview
Current Medicinal Chemistry Current Biology of MTP: Implications for Selective Inhibition
Current Topics in Medicinal Chemistry Treatment of Takotsubo Cardiomyopathy
Current Pharmaceutical Design Fetal Risks of Maternal Diabetes
Current Women`s Health Reviews PDE5 Inhibitor Treatment Options for Urologic and Non-Urologic Indications: 2012 Update
Current Pharmaceutical Design Perioperative Considerations in Diabetic Patients
Current Diabetes Reviews Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients
Current Pharmaceutical Design Inflammatory Mediators and the Failing Heart: A Translational Approach
Current Molecular Medicine Advent and Maturation of Regenerative Medicine
Current Stem Cell Research & Therapy Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy
Current Cardiology Reviews A Practical Comprehensive Approach to Management of Acute Decompensated Heart Failure
Current Cardiology Reviews Cardiotoxicity of Tyrosine-Kinase-Targeting Drugs
Cardiovascular & Hematological Agents in Medicinal Chemistry Cellular Strategies to Combat Protein Misfolding: Intricate Role of Hsp70 in Stress Management
Current Chemical Biology Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases
Current Pharmaceutical Design