N-acetylcysteine in Psychiatric Disorders: Possible Role of Cysteinet Deregulation

Martínez-Banaclocha, Marcos

doi:10.9734/indj/2018/44483

Cited by 4 publications

(3 citation statements)

References 32 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that cysteinet is crucial in neurodegeneration [ 1 , 2 , 3 , 4 , 5 ] and brain development, which is also under the control of SCCPs at very early stages [ 27 ]. Further investigations may be necessary to better understand psychiatric diseases, such as schizophrenia and bipolar disorders [ 28 , 29 ].…”

Section: The Sensitive-cysteine Redox Proteome (Cysteinet)mentioning

confidence: 99%

“…Any substance that can modulate the redox proteome must, therefore, be regarded as medication with significant restorative ability but potential elevated secondary consequences due to its interference with highly controlled biological mechanisms. We have proposed the probable usefulness of NAC on the redox regulation of SCCPs involved in a broad spectrum of pathways implicated in neurodegenerative and psychiatric diseases [ 1 , 2 , 3 , 4 , 5 , 29 , 37 , 187 , 343 , 344 , 345 , 346 , 347 , 348 , 349 , 350 , 351 ]. NAC is a safe pro-substrate of cysteine that can repair redox disregulated states for diverse sensitive-cysteine-bearing proteins involved in many pathways ( Figure 4 ).…”

Section: Modulation Of Cysteinet By N -Acetyl-cyst...mentioning

confidence: 99%

See 1 more Smart Citation

N-Acetyl-Cysteine: Modulating the Cysteine Redox Proteome in Neurodegenerative Diseases

Martínez-Banaclocha

2022

Antioxidants

View full text Add to dashboard Cite

In the last twenty years, significant progress in understanding the pathophysiology of age-associated neurodegenerative diseases has been made. However, the prevention and treatment of these diseases remain without clinically significant therapeutic advancement. While we still hope for some potential genetic therapeutic approaches, the current reality is far from substantial progress. With this state of the issue, emphasis should be placed on early diagnosis and prompt intervention in patients with increased risk of neurodegenerative diseases to slow down their progression, poor prognosis, and decreasing quality of life. Accordingly, it is urgent to implement interventions addressing the psychosocial and biochemical disturbances we know are central in managing the evolution of these disorders. Genomic and proteomic studies have shown the high molecular intricacy in neurodegenerative diseases, involving a broad spectrum of cellular pathways underlying disease progression. Recent investigations indicate that the dysregulation of the sensitive-cysteine proteome may be a concurrent pathogenic mechanism contributing to the pathophysiology of major neurodegenerative diseases, opening new therapeutic opportunities. Considering the incidence and prevalence of these disorders and their already significant burden in Western societies, they will become a real pandemic in the following decades. Therefore, we propose large-scale investigations, in selected groups of people over 40 years of age with decreased blood glutathione levels, comorbidities, and/or mild cognitive impairment, to evaluate supplementation of the diet with low doses of N-acetyl-cysteine, a promising and well-tolerated therapeutic agent suitable for long-term use.

show abstract

Section: The Sensitive-cysteine Redox Proteome (Cysteinet)mentioning

confidence: 99%

Section: Modulation Of Cysteinet By N -Acetyl-cyst...mentioning

confidence: 99%

N-Acetyl-Cysteine: Modulating the Cysteine Redox Proteome in Neurodegenerative Diseases

Martínez-Banaclocha

2022

Antioxidants

View full text Add to dashboard Cite

show abstract

“…Unlike GSH, NAC has better oral and topical bioavailability, and has been commercially accessible for a long time [17]. We suggested that NAC regulates SCCPs in a comprehensive range of pathways involved in neurodegenerative and psychiatric disorders [17,[20][21][22][23][24]41,[191][192][193][194][195][196][197][198][199][200][201][202][203]. Moreover, NAC may work synergistically with other supplemental nutrients, such as glycine [204].…”

Section: Nac Bioavailability and Safetymentioning

confidence: 99%

Targeting the Cysteine Redox Proteome in Parkinson’s Disease: The Role of Glutathione Precursors and Beyond

Martínez-Banaclocha

2023

Antioxidants

View full text Add to dashboard Cite

Encouraging recent data on the molecular pathways underlying aging have identified variants and expansions of genes associated with DNA replication and repair, telomere and stem cell maintenance, regulation of the redox microenvironment, and intercellular communication. In addition, cell rejuvenation requires silencing some transcription factors and the activation of pluripotency, indicating that hidden molecular networks must integrate and synchronize all these cellular mechanisms. Therefore, in addition to gene sequence expansions and variations associated with senescence, the optimization of transcriptional regulation and protein crosstalk is essential. The protein cysteinome is crucial in cellular regulation and plays unexpected roles in the aging of complex organisms, which show cumulative somatic mutations, telomere attrition, epigenetic modifications, and oxidative dysregulation, culminating in cellular senescence. The cysteine thiol groups are highly redox-active, allowing high functional versatility as structural disulfides, redox-active disulfides, active-site nucleophiles, proton donors, and metal ligands to participate in multiple regulatory sites in proteins. Also, antioxidant systems control diverse cellular functions, including the transcription machinery, which partially depends on the catalytically active cysteines that can reduce disulfide bonds in numerous target proteins, driving their biological integration. Since we have previously proposed a fundamental role of cysteine-mediated redox deregulation in neurodegeneration, we suggest that cellular rejuvenation of the cysteine redox proteome using GSH precursors, like N-acetyl-cysteine, is an underestimated multitarget therapeutic approach that would be particularly beneficial in Parkinson’s disease.

show abstract

Proteomic Complexity in Parkinson’s Disease: A Redox Signaling Perspective of the Pathophysiology and Progression

Martínez-Banaclocha

2021

Neuroscience

View full text Add to dashboard Cite

N-acetylcysteine in Psychiatric Disorders: Possible Role of Cysteinet Deregulation

Cited by 4 publications

References 32 publications

N-Acetyl-Cysteine: Modulating the Cysteine Redox Proteome in Neurodegenerative Diseases

N-Acetyl-Cysteine: Modulating the Cysteine Redox Proteome in Neurodegenerative Diseases

Targeting the Cysteine Redox Proteome in Parkinson’s Disease: The Role of Glutathione Precursors and Beyond

Proteomic Complexity in Parkinson’s Disease: A Redox Signaling Perspective of the Pathophysiology and Progression

Contact Info

Product

Resources

About