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

Martínez-Banaclocha, Marcos

doi:10.1016/j.neuroscience.2020.11.006

Cited by 7 publications

(33 citation statements)

References 134 publications

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“…GSH is a sensitive-cysteine-bearing tripeptide, which is dependent on the cysteine/cystine pro-portion and the redox micro-environmental balance, regulating diverse protein functions by S-glutathionylation. NAC is a unique substance that has beneficial impacts in brain aging and neurodegenerative diseases, not only via classical antioxidant properties, but also, and even more importantly, enabling the repair and supervision of the cellular redox equilibrium through the modulation of the sensitive-cysteine network of intracellular and extracellular proteins (Figure 4) [1][2][3][4][5]. NAC is a membrane penetrable cysteine prodrug that regenerates total glutathione status and reduces excessive oxidized glutathione concentrations.…”

Section: Modulation Of Cysteinet By N-acetyl-cysteine (Nac)mentioning

confidence: 99%

“…Furthermore, NAC treatments have a healthy impact on multiple other conditions, including oncological and cardiovascular diseases, ophthalmic diseases, HIV conditions, metal toxicity, cerebral ischemic and bleeding disorders, traumatic brain damage, and even neuropsychiatric disorders [355][356][357][358]. NAC is a unique substance that has beneficial impacts in brain aging and neurodegenerative diseases, not only via classical antioxidant properties, but also, and even more importantly, enabling the repair and supervision of the cellular redox equilibrium through the modulation of the sensitive-cysteine network of intracellular and extracellular proteins (Figure 4) [1][2][3][4][5]. NAC is a membrane penetrable cysteine prodrug that regenerates total glutathione status and reduces excessive oxidized glutathione concentrations.…”

Section: Modulation Of Cysteinet By N-acetyl-cysteine (Nac)mentioning

confidence: 99%

“…Sensitive-cysteines can suffer various redox changes (e.g., s-glutathionylation, s-nitrosylation, sulfenylation, disulfide bond formation) under particular physiological or pathological conditions, resulting in a reversible shift in protein function [ 1 ]. 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%

“…We have previously proposed that some common neurodegenerative disorders, such as AD and PD, each involve the dysregulation of the sensitive-cysteine proteome [ 1 , 2 , 3 , 4 , 5 ]. In the present paper, we extend this proposition to other neurodegenerative diseases, suggesting that a disturbance of the redox cysteine proteome mediates all age-associated degenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

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

Martínez-Banaclocha

2022

Antioxidants

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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.

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Section: Modulation Of Cysteinet By N-acetyl-cysteine (Nac)mentioning

confidence: 99%

Section: Modulation Of Cysteinet By N-acetyl-cysteine (Nac)mentioning

confidence: 99%

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

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Martínez-Banaclocha

2022

Antioxidants

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“…It has been found that 28 sets of genes are linked to PD, likely playing a pathogenic role at the early stages of the disease (Anderson and Becker, 1981;Zheng et al, 2010;Keane et al, 2011). Currently, a more extensive list of genes is associated with the onset of PD, supporting the multifactorial etiology of both familial and sporadic cases of PD (Scott et al, 2017;Lu et al, 2018;Zeng et al, 2018;Kline et al, 2020;Wang et al, 2020b;Allende et al, 2021;Martinez-Banaclocha, 2021).…”

Section: Molecular Mechanisms Associated With Pdmentioning

confidence: 99%

Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease

2021

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Parkinson’s disease (PD) is a neurodegenerative condition characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) in the midbrain resulting in progressive impairment in cognitive and motor abilities. The physiological and molecular mechanisms triggering dopaminergic neuronal loss are not entirely defined. PD occurrence is associated with various genetic and environmental factors causing inflammation and mitochondrial dysfunction in the brain, leading to oxidative stress, proteinopathy, and reduced viability of dopaminergic neurons. Oxidative stress affects the conformation and function of ions, proteins, and lipids, provoking mitochondrial DNA (mtDNA) mutation and dysfunction. The disruption of protein homeostasis induces the aggregation of alpha-synuclein (α-SYN) and parkin and a deficit in proteasome degradation. Also, oxidative stress affects dopamine release by activating ATP-sensitive potassium channels. The cholinergic system is essential in modulating the striatal cells regulating cognitive and motor functions. Several muscarinic acetylcholine receptors (mAChR) and nicotinic acetylcholine receptors (nAChRs) are expressed in the striatum. The nAChRs signaling reduces neuroinflammation and facilitates neuronal survival, neurotransmitter release, and synaptic plasticity. Since there is a deficit in the nAChRs in PD, inhibiting nAChRs loss in the striatum may help prevent dopaminergic neurons loss in the striatum and its pathological consequences. The nAChRs can also stimulate other brain cells supporting cognitive and motor functions. This review discusses the cholinergic system as a therapeutic target of cotinine to prevent cognitive symptoms and transition to dementia in PD.

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Nanoplastics induce neuroexcitatory symptoms in zebrafish (Danio rerio) larvae through a manner contrary to Parkinsonian's way in proteomics

Wang,

Cong

et al. 2023

Science of The Total Environment

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

Cited by 7 publications

References 134 publications

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

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

Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease

Nanoplastics induce neuroexcitatory symptoms in zebrafish (Danio rerio) larvae through a manner contrary to Parkinsonian's way in proteomics

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