Reference | [1]. Molecules. 2018 Dec 13;23(12):3305. doi: 10.3390/molecules23123305.<br />
Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases.<br />
Tardiolo G(1), Bramanti P(2), Mazzon E(3).<br />
Author information: (1)IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. [email protected]. (2)IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. [email protected]. (3)IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy. [email protected].<br />
N-acetylcysteine (NAC), which is an acetylated cysteine compound, has aroused scientific interest for decades due to its important medical applications. It also represents a nutritional supplement in the human diet. NAC is a glutathione precursor and shows antioxidant and anti-inflammatory activities. In addition to the uses quoted in the literature, NAC may be considered helpful in therapies to counteract neurodegenerative and mental health diseases. Furthermore, this compound has been evaluated for its neuroprotective potential in the prevention of cognitive aging dementia. NAC is inexpensive, commercially available and no relevant side effects were observed after its administration. The purpose of this paper is to give an overview on the effects and applications of NAC in Parkinson's and Alzheimer's disorders and in neuropathic pain and stroke.<br />
DOI: 10.3390/molecules23123305 PMCID: PMC6320789 PMID: 30551603<br />
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[2]. Biochim Biophys Acta. 2013 Aug;1830(8):4117-29. doi: 10.1016/j.bbagen.2013.04.016. Epub 2013 Apr 22.<br />
The chemistry and biological activities of N-acetylcysteine.<br />
Samuni Y(1), Goldstein S, Dean OM, Berk M.<br />
Author information: (1)Deakin University, Geelong, Australia.<br />
BACKGROUND: N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders. SCOPE OF REVIEW: The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry. MAJOR CONCLUSIONS: The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3(-) and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis. GENERAL SIGNIFICANCE: The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood-brain barrier as well as elucidating its reactions with components of cell signaling pathways.<br />
DOI: 10.1016/j.bbagen.2013.04.016 PMID: 23618697 [Indexed for MEDLINE]<br />
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[3]. Neurosci Biobehav Rev. 2015 Aug;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015. Epub 2015 May 6.<br />
Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review.<br />
Deepmala(1), Slattery J(2), Kumar N(3), Delhey L(2), Berk M(4), Dean O(4), Spielholz C(5), Frye R(2).<br />
Author information: (1)Arkansas Children's Hospital, Little Rock, AR, United States; Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, United States. Electronic address: [email protected]. (2)Arkansas Children's Hospital, Little Rock, AR, United States; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States. (3)Arkansas Children's Hospital, Little Rock, AR, United States; Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, United States. (4)Florey Institute of Neuroscience and Mental Health, Department of Psychiatry, and Orygen, The National Centre of Excellence in Youth Mental Health, University of Melbourne, Parkville, Australia; IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Victoria, Australia. (5)BioAdvantex Pharma Inc., MaRS Discovery District, Toronto, ON, Canada.<br />
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.<br />
DOI: 10.1016/j.neubiorev.2015.04.015 PMID: 25957927<br />
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[4]. Expert Opin Drug Metab Toxicol. 2017 Mar;13(3):279-292. doi: 10.1080/17425255.2017.1251580. Epub 2016 Nov 2.<br />
N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects.<br />
Minarini A(1), Ferrari S(1), Galletti M(1), Giambalvo N(1), Perrone D(1), Rioli G(1), Galeazzi GM(1).<br />
Author information: (1)a Department of Diagnostic-Clinical Medicine and Public Health , University of Modena and Reggio Emilia , Modena , Italy.<br />
N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder. Promising results were found in trials testing the use of NAC, mainly as an add-on treatment, in cannabis use disorder in young people, depression in bipolar disorder, negative symptoms in schizophrenia, and excoriation (skin-picking) disorder. Despite initial optimism, recent findings regarding NAC efficacy in autism have been disappointing. Expert opinion: These preliminary positive results require further confirmation in larger samples and with longer follow-ups. Given its high tolerability and wide availability, NAC represents an important target to investigate in the field of new adjunctive treatments for psychiatric conditions.<br />
DOI: 10.1080/17425255.2017.1251580 PMID: 27766914<br />
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[5]. Biomed Res Int. 2018 Oct 22;2018:2469486. doi: 10.1155/2018/2469486. eCollection 2018.<br />
N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence.<br />
Ooi SL(1), Green R(2), Pak SC(2).<br />
Author information: (1)Centre for Complementary & Alternative Medicine, Singapore 247909, Singapore. (2)School of Biomedical Sciences, Charles Sturt University, Bathurst, NSW 2795, Australia.<br />
N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia. N-acetylcysteine also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.<br />
DOI: 10.1155/2018/2469486 PMCID: PMC6217900 PMID: 30426004
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