Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re‐establishing autophagic flux via promoting leptin signalling in a 6‐hydroxydopamine rat model of Parkinson's disease

Wu, Jiang; Zou, Wei; Hu, Min; Tian, Qing; Fan, Xuemei; Li, Min; Zhang, Ping; Chen, Yongjun; Jiang, Jiamei

doi:10.1111/1440-1681.13587

Cited by 14 publications

(6 citation statements)

References 77 publications

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“…Although several reports have demonstrated the involvement of MA in hydrogen sulfide-mediated neuroprotection, the effects of hydrogen sulfide on MA are also controversial [ 35 , 36 ]. Several studies have revealed that hydrogen sulfide exerts neuroprotective effects via the activation of MA [ 37 , 38 ], while MA inhibition contributes to the hydrogen sulfide-mediated neuroprotection [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation

Ueda

Ohta

Konno

et al. 2022

Cells

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Chaperone-mediated autophagy (CMA) is a pathway in the autophagy-lysosome protein degradation system. CMA impairment has been implicated to play a role in spinocerebellar ataxia (SCA) pathogenesis. D-cysteine is metabolized by D-amino acid oxidase (DAO), leading to hydrogen sulfide generation in the cerebellum. Although D-cysteine alleviates the disease phenotypes in SCA-model mice, it remains unknown how hydrogen sulfide derived from D-cysteine exerts this effect. In the present study, we investigated the effects of D-cysteine and hydrogen sulfide on CMA activity using a CMA activity marker that we have established. D-cysteine activated CMA in Purkinje cells (PCs) of primary cerebellar cultures where DAO was expressed, while it failed to activate CMA in DAO-deficient AD293 cells. In contrast, Na2S, a hydrogen sulfide donor, activated CMA in both PCs and AD293 cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to be activated by hydrogen sulfide and regulate CMA activity. An Nrf2 inhibitor, ML385, prevented CMA activation triggered by D-cysteine and Na2S. Additionally, long-term treatment with D-cysteine increased the amounts of Nrf2 and LAMP2A, a CMA-related protein, in the mouse cerebellum. These findings suggest that hydrogen sulfide derived from D-cysteine enhances CMA activity via Nrf2 activation.

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Section: Discussionmentioning

confidence: 99%

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation

Ueda

Ohta

Konno

et al. 2022

Cells

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“…Experimental data connect metabolic deterioration and Parkinson’s disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by several adipokines, particularly by leptin. Leptin had protective effects in an experimental model of PD, generated by a mitochondrial neurotoxin [ 114 ], and compounds that increase leptin signaling in a 6-hydroxydopamine rat model of PD attenuate neuronal apoptosis of substantia nigra [ 115 ].…”

Section: Functionality Of Leptin and Its Involvement In Pathologymentioning

confidence: 99%

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Casado

Collado-Pérez

Frago

et al. 2023

IJMS

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Excess body weight is frequently associated with low-grade inflammation. Evidence indicates a relationship between obesity and cancer, as well as with other diseases, such as diabetes and non-alcoholic fatty liver disease, in which inflammation and the actions of various adipokines play a role in the pathological mechanisms involved in these disorders. Leptin is mainly produced by adipose tissue in proportion to fat stores, but it is also synthesized in other organs, where leptin receptors are expressed. This hormone performs numerous actions in the brain, mainly related to the control of energy homeostasis. It is also involved in neurogenesis and neuroprotection, and central leptin resistance is related to some neurological disorders, e.g., Parkinson’s and Alzheimer’s diseases. In peripheral tissues, leptin is implicated in the regulation of metabolism, as well as of bone density and muscle mass. All these actions can be affected by changes in leptin levels and the mechanisms associated with resistance to this hormone. This review will present recent advances in the molecular mechanisms of leptin action and their underlying roles in pathological situations, which may be of interest for revealing new approaches for the treatment of diseases where the actions of this adipokine might be compromised.

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“…On the other hand, the exogenous application of H 2 S promoted the increase in endogenous H 2 S and inhibited the movement disorder by reversing the depletion of tyrosine–hydroxylase-positive neurons in the SN. This protective effect may be mediated by promoting leptin signaling and increasing malondialdehyde levels in the striatum [ 110 , 111 ]. NaHS application could also protect SH-SY5Y cells against 1-methyl-4-phenylpyridinium ion (MPP + )-induced mitochondrial transmembrane potential loss, oxidative stress and cell apoptotic in the PD cell model [ 109 ].…”

Section: Involvement Of H 2 S In Neurological Dise...mentioning

confidence: 99%

Advances of H2S in Regulating Neurodegenerative Diseases by Preserving Mitochondria Function

Zhou

Wang

2023

Antioxidants

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Neurotoxicity is induced by different toxic substances, including environmental chemicals, drugs, and pathogenic toxins, resulting in oxidative damage and neurodegeneration in mammals. The nervous system is extremely vulnerable to oxidative stress because of its high oxygen demand. Mitochondria are the main source of ATP production in the brain neuron, and oxidative stress-caused mitochondrial dysfunction is implicated in neurodegenerative diseases. H2S was initially identified as a toxic gas; however, more recently, it has been recognized as a neuromodulator as well as a neuroprotectant. Specifically, it modulates mitochondrial activity, and H2S oxidation in mitochondria produces various reactive sulfur species, thus modifying proteins through sulfhydration. This review focused on highlighting the neuron modulation role of H2S in regulating neurodegenerative diseases through anti-oxidative, anti-inflammatory, anti-apoptotic and S-sulfhydration, and emphasized the importance of H2S as a therapeutic molecule for neurological diseases.

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Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re‐establishing autophagic flux via promoting leptin signalling in a 6‐hydroxydopamine rat model of Parkinson's disease

Cited by 14 publications

References 77 publications

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

Advances of H2S in Regulating Neurodegenerative Diseases by Preserving Mitochondria Function

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