Multifaced role of protein deacetylase sirtuins in neurodegenerative disease. (January 2022)

• Record Type: Journal Article
• Authors: Gupta, Rohan; Ambasta, Rashmi K.; Kumar, Pravir
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 132(2022)
• Page Start: 976
• Page End: 997
• Publication Date: 2022-01
• Subjects: AD Alzheimer's Disease -- AdipoR1 adiponectin receptor 1 -- ADP adenosine diphosphate -- Akt protein kinase B -- ALS Amyotrophic Lateral Sclerosis -- AMPARs α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors -- AMPK 5′ adenosine monophosphate-activated protein kinase -- AP-1 activator protein 1 -- APP amyloid protein precursor -- Aβ amyloid-beta -- BDNF brain derived neurotrophic factor -- BSYZ Bushen-Yizhi -- CD38 cyclic ADP-ribose cyclase/cluster of differentiation 38 -- CPS1 carbamoyl phosphate synthetase 1 -- CR calorie restriction -- CREB cAMP response element-binding protein -- DDIT3 DNA Damage-Inducible Transcript 3 Protein -- ER endoplasmic reticulum -- ERRα estrogen-related receptor alpha -- ETC electron transport chain -- EX-527 6-chloro-2, 3, 4, 9-tetrahydro-1H-carbazole-1-carboxamide -- FAO fatty acid oxidation -- FoxO forkhead box O -- FOXO3A Forkhead Box O3 A -- FZS fuzhisan -- GDNF glial cell line-derived neurotrophic factor -- GM1 monosialoganglioside -- GSH glutathione -- GSK3β glycogen synthase kinase 3 beta -- H2O2 hydrogen peroxide -- HADHA hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha -- HD Huntington's Disease -- HIF-1α hypoxia inducible factor alpha 1 -- HKL Honokiol -- HMGCS1 hydroxymethylglutaryl-CoA synthase -- IL-1β interleukin-1β -- IRF3 Interferon Regulatory Factor 3 -- IκBα inhibitor of nuclear factor kappa B -- JAK2 janus kinase 2 -- KO knock-out -- LKB1 liver kinase B1 -- LONP1 lon protease-like protein -- MCCC methylcrotonyl-CoA carboxylase complex -- MCD malonyl-CoA decarboxylase -- miR micro RNA -- MMP mitochondrial membrane potential -- MnSOD manganese superoxide dismutase -- MPP+ 1-methyl-4-phenylpyridinium ion -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- MRPL10 mitochondrial ribosomal protein L10 -- mtDNA mitochondrial DNA -- NaAD nicotinic acid dinucleotide -- NAC N-acetylcysteine -- NAD nicotinamide adenine dinucleotide -- NADPH nicotinamide adenine dinucleotide phosphate -- NaHS sodium hydrosulfide -- NaMN nicotinic acid mononucleotide -- NAMPT nicotinamide phosphoribosyl transferase I-III -- N-CoR nuclear receptor corepressor -- NDDs neurodegenerative diseases -- NDUFA9 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 -- NF-κβ nuclear factor kappa-light-chain-enhancer of activated B cells -- NLRP3 NLR Family Pyrin Domain Containing 3 -- NMN nicotinamide mononucleotide -- NMNATs NMN/NaMN adenylyl transferase -- Nrf2 nuclear factor erythroid 2-related factor 2 -- OGD oxygen and glucose deprivation -- OGG1 8-oxoguanine-DNA-glycosylase-1 -- OXPHOS oxidative phosphorylation -- PARPs poly(ADP-ribose) polymerases -- PD Parkinson's Disease -- PDH pyruvate dehydrogenase -- PGC-1α PPARG coactivator 1 alpha -- PPARα peroxisome proliferator-activated receptor alpha -- RBP RNA binding proteins -- REST RE1-silencing transcription factor -- ROCK1 serine/threonine Rho kinase 1 -- ROS reactive oxygen species -- SDH Succinate dehydrogenase -- SOD2 superoxide dismutatase -- SREBP2 sterol regulatory element-binding protein 2 -- STAT3 signal transducer and activator of transcription 3 -- TCA tricarboxylic acid cycle -- TJP1 Tight junction protein ZO-1 -- TLR4 toll-like receptor 4 -- TNF-α tumor necrosis factor-α -- TrkB tyrosine receptor kinase B -- VGLUT1 vesicular glutamate transporter 1 -- WHC woohwangcheongsimwon -- YY1 Yin and Yang 1 -- ω-3 PUFA Omega-3 polyunsaturated fatty acids; Sirtuins -- Neurodegenerative disease -- Synaptic plasticity -- Mitochondrial biogenesis -- Sirtuins modulators; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2021.10.047
• Languages: English
• ISSNs: 0149-7634

Abstract

Graphical abstract: Class III histone deacetylases, also known as sirtuins (SIRT1−7), are involved in regulating cellular and biological functions such as apoptosis, autophagy, inflammatory response, mitochondrial dysfunction, oxidative stress, and DNA damage. Sirtuins are also involved in the pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). However, the underlying mechanism of sirtuins expression in the case of neurodegeneration is still an area of extensive research. Some studies exhibit that overexpression of sirtuins is neuroprotective, while others demonstrated that inhibition of sirtuins with specific inhibitors or natural compounds ameliorates neurotoxic effects. In the case of AD, overexpression of SIRT1 is neuroprotective, while genetic deletion of SIRT6 is neurotoxic. Similarly, in PD cases, SIRT1 overexpression and SIRT2 inhibition ameliorate neurotoxic effects, while SIRT3 and SIRT5 deletion have detrimental or neurotoxic functions. SIRT1 overexpression has neuroprotective effects in ALS and HD, while SIRT2 inhibition has a protective role in HD but is unexplored in ALS. Highlights: SIRT plays an effective role in mitochondrial biogenesis and aging process. SIRT is involved in neural differentiation, neurogenesis, neural plasticity, and cognitive function. Sirtuins has a role in autophagic degradation, apoptosis, and neuroinflammatory response. SIRT has ability to correct excitotoxic and degenerative brain disorders. Sirtuins modulators and micro-RNAs as an active therapeutic agent for neurodegenerative diseases. Abstract: Sirtuins, a class III histone/protein deacetylase, is a central regulator of metabolic function and cellular stress response. This plays a pivotal role in the pathogenesis and progression of diseases such as cancer, neurodegeneration, metabolic syndromes, and cardiovascular disease. Sirtuins regulate biological and cellular processes, for instance, mitochondrial biogenesis, lipid and fatty acid oxidation, oxidative stress, gene transcriptional activity, apoptosis, inflammatory response, DNA repair mechanism, and autophagic cell degradation, which are known components for the progression of the neurodegenerative diseases (NDDs). Emerging evidence suggests that sirtuins are the useful molecular targets against NDDs like, Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), and Amyotrophic Lateral Sclerosis (ALS). However, the exact mechanism of neuroprotection mediated through sirtuins remains unsettled. The manipulation of sirtuins activity with its modulators, calorie restriction (CR), and micro RNAs (miR) is a novel therapeutic approach for the treatment of NDDs. Herein, we reviewed the current putative therapeutic role of sirtuins in regulating synaptic plasticity and cognitive functions, which are mediated through the different molecular phenomenon to prevent neurodegeneration. We also explained the implications of sirtuin modulators, and miR based therapies for the treatment of life-threatening NDDs.