Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders

Nakamura, Tomohiro; Oh, Chang-ki; Zhang, Xu; Tannenbaum, Steven R.; Lipton, Stuart A.

doi:10.1089/ars.2021.0081

Cited by 23 publications

(17 citation statements)

References 192 publications

(314 reference statements)

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“…p-tau also interacts with Drp1 and enhances GTPase Drp1 enzymatic activity, leading to excessive fragmentation of mitochondria and mitochondrial dysfunction in AD [ 98 ]. A Drp1 S-nitrosylation adduct (SNO-Drp1), further stimulated its activity, and led to excessive mitochondrial fragmentation, and synapse loss [ 99 ].…”

Section: Dependence Of Mitochondrial Fission and Fusion On Gtpmentioning

confidence: 99%

GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease

et al. 2023

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Increased interest in the aging and Alzheimer’s disease (AD)-related impairments in autophagy in the brain raise important questions about regulation and treatment. Since many steps in endocytosis and autophagy depend on GTPases, new measures of cellular GTP levels are needed to evaluate energy regulation in aging and AD. The recent development of ratiometric GTP sensors (GEVALS) and findings that GTP levels are not homogenous inside cells raise new issues of regulation of GTPases by the local availability of GTP. In this review, we highlight the metabolism of GTP in relation to the Rab GTPases involved in formation of early endosomes, late endosomes, and lysosomal transport to execute the autophagic degradation of damaged cargo. Specific GTPases control macroautophagy (mitophagy), microautophagy, and chaperone-mediated autophagy (CMA). By inference, local GTP levels would control autophagy, if not in excess. Additional levels of control are imposed by the redox state of the cell, including thioredoxin involvement. Throughout this review, we emphasize the age-related changes that could contribute to deficits in GTP and AD. We conclude with prospects for boosting GTP levels and reversing age-related oxidative redox shift to restore autophagy. Therefore, GTP levels could regulate the numerous GTPases involved in endocytosis, autophagy, and vesicular trafficking. In aging, metabolic adaptation to a sedentary lifestyle could impair mitochondrial function generating less GTP and redox energy for healthy management of amyloid and tau proteostasis, synaptic function, and inflammation.

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Section: Dependence Of Mitochondrial Fission and Fusion On Gtpmentioning

confidence: 99%

GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease

et al. 2023

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“…Protein S-nitrosylation levels can also depend on denitrosylation reactions consisting in enzymatic or non-enzymatic cleavage of S-nitrosyl group from Cys [ 89 ]. Although the intracellular S-nitrosylation protein level is relatively low, it has been linked to pathological conditions in different ways [ 90 , 91 , 92 ]. S-nitrosylation can regulate at least 3000 proteins involved in different biological processes.…”

Section: Oxidative Stress (General Concepts)mentioning

confidence: 99%

Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles

Chiaradia

Tancini

Emiliani

et al. 2021

Cells

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Under physio-pathological conditions, cells release membrane-surrounded structures named Extracellular Vesicles (EVs), which convey their molecular cargo to neighboring or distant cells influencing their metabolism. Besides their involvement in the intercellular communication, EVs might represent a tool used by cells to eliminate unnecessary/toxic material. Here, we revised the literature exploring the link between EVs and redox biology. The first proof of this link derives from evidence demonstrating that EVs from healthy cells protect target cells from oxidative insults through the transfer of antioxidants. Oxidative stress conditions influence the release and the molecular cargo of EVs that, in turn, modulate the redox status of target cells. Oxidative stress-related EVs exert both beneficial or harmful effects, as they can carry antioxidants or ROS-generating enzymes and oxidized molecules. As mediators of cell-to-cell communication, EVs are also implicated in the pathophysiology of oxidative stress-related diseases. The review found evidence that numerous studies speculated on the role of EVs in redox signaling and oxidative stress-related pathologies, but few of them unraveled molecular mechanisms behind this complex link. Thus, the purpose of this review is to report and discuss this evidence, highlighting that the analysis of the molecular content of oxidative stress-released EVs (reminiscent of the redox status of originating cells), is a starting point for the use of EVs as diagnostic and therapeutic tools in oxidative stress-related diseases.

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“…In Liu et al's study, E2 and X-linked inhibitors of apoptosis protein (XIAP) were increased, and FSH was decreased with MBD treatment [ 38 ]. XIAP could bind to the apoptosis initiator caspase-9, and apoptosis effectors caspase-3 and caspases-7, to down-regulate apoptosis [ 45 ]. Therefore, Liu speculated that MBD could regulate apoptosis and play a therapeutic role in POF by regulating XIAP.…”

Section: Application Of Traditional Chinese Medicine In Pofmentioning

confidence: 99%

Beneficial Effects of Traditional Chinese Medicine in the Treatment of Premature Ovarian Failure

Xiao

Wei³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Premature ovarian failure (POF) is characterized by hormonal disorders, amenorrhea, and premature loss of fertility potential in women of reproductive age. Several studies have been conducted on the effectiveness of traditional Chinese medicine (TCM) in treating POF. TCM relied primarily on apoptosis, immunity, and aging to treat POF based on the studies of domestic and foreign literature. Zuogui pills inhibited mitochondrial-dependent apoptosis in the treatment of POF. Huyang Yangkun formula regulated the downstream of the Bcl-2 family to resist apoptosis through the aquaporin-1 protein. Modified Bazhen decoction regulated apoptosis in POF by regulating X-linked inhibitors of apoptosis protein. Bushen Tianjing recipe was effective in treating POF by promoting angiogenesis and preventing apoptosis. As for immunity, Bushen Jianpi prescription and Er-Xian decoction cured autoimmunity POF models and increased follicular development-related protein expression. Bushen Huoxue Tang improved ovarian function and reduced ovarian inflammation by regulating the Nrf2/Keap1 signaling pathway and T lymphocytes. Taohong Siwu decoction promoted the proliferation and differentiation of granulosa cells of POF mice by regulating the TGF-β1/Smads signaling pathway. In addition, ginsenoside Rg1 and Jiajian Guisheng formula treated POF by regulating cell aging-related mechanisms. Si Wu Tang treated POF by activating the angiogenesis-related proteins. The goal of this review is to serve as a reference for in-depth research into the treatment of POF with TCM and provide inspiration for new diagnostic methods and treatment options.

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Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders

Cited by 23 publications

References 192 publications

GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease

GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease

Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles

Beneficial Effects of Traditional Chinese Medicine in the Treatment of Premature Ovarian Failure

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