Glutamatergic neurotransmission: A potential pharmacotherapeutic target for the treatment of cognitive disorders

Chakraborty, Pratik; Dey, Abhijit; Gopalakrishnan, Abilash Valsala; Kumari, Swati; Ojha, Shreesh; Prakash, Anand; Kumar, Dhruv; Ambasta, Rashmi K.; Jha, Niraj Kumar; Dewanjee, Saikat; Jha, Saurabh

doi:10.1016/j.arr.2022.101838

Cited by 19 publications

(7 citation statements)

References 310 publications

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“…Calcium overload is another important pathological mechanism associated with AD [98,99]. Ca 2+ overload has been reported to cause a range of neuronal injuries, with intracellular Ca 2+ overload triggering neuroinflammation, cytochrome C release, and apoptosis [100], and elevated intracellular free Ca 2+ levels also mediating the activation of Ca 2+ -dependent enzymes.…”

Section: Discussionmentioning

confidence: 99%

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms

Liu,

Chen,

Zhao

et al. 2023

Molecules

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Neurological-related disorders are diseases that affect the body’s neurons or peripheral nerve tissue, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

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Section: Discussionmentioning

confidence: 99%

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms

Liu,

Chen,

Zhao

et al. 2023

Molecules

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“…The suppression of the glutamatergic system has been associated with cognitive dysfunction. Pro-inflammatory cytokine IL-1β inhibits glutamate release in presynaptic terminals and impairs memory consolidation by activating p38MAPK, inhibiting ERK phosphorylation and calcium influx ( Kelly et al, 2003 ; Gonzalez et al, 2013 ; Machado et al, 2015 ; Chakraborty et al, 2023 ). It has been observed that excessive IL-1β also suppresses the function and expression of glutamatergic receptors in sepsis models.…”

Section: Il-1β Impairs Cognitive Function After Sepsismentioning

confidence: 99%

IL-1β, the first piece to the puzzle of sepsis-related cognitive impairment?

Zhu,

Wan,

Huang

et al. 2024

Front. Neurosci.

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Sepsis is a leading cause of death resulting from an uncontrolled inflammatory response to an infectious agent. Multiple organ injuries, including brain injuries, are common in sepsis. The underlying mechanism of sepsis-associated encephalopathy (SAE), which is associated with neuroinflammation, is not yet fully understood. Recent studies suggest that the release of interleukin-1β (IL-1β) following activation of microglial cells plays a crucial role in the development of long-lasting neuroinflammation after the initial sepsis episode. This review provides a comprehensive analysis of the recent literature on the molecular signaling pathways involved in microglial cell activation and interleukin-1β release. It also explores the physiological and pathophysiological role of IL-1β in cognitive function, with a particular focus on its contribution to long-lasting neuroinflammation after sepsis. The findings from this review may assist healthcare providers in developing novel interventions against SAE.

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“…As the most important excitatory neurotransmitter in the brain, glutamate binds to ionotropic receptors (e.g., N-methyl-D aspartate receptors (NMDAR) and non-NMDA receptors) and metabotropic glutamate receptors (mGluRs) ( Zhang et al, 2022 ; Moller, 2023 ). The former mediates the process of rapid excitatory synaptic transmission through the formation of receptor-channel complexes, while the latter exerts its biological effects through the activation of coupled G-proteins to generate second messengers ( Chakraborty et al, 2023 ). A robust literature supports the role of metabotropic glutamate receptor type 5 (mGluR5) and ionotropic receptors in the pathophysiology of cognitive impairment ( Sitcheran et al, 2005 ; Shah et al, 2012 ; Ceprian and Fulton, 2019 ; Chen Y. et al, 2023 ).…”

Section: Mechanisms By Which Peripheral Inflammation Promotes Central...mentioning

confidence: 99%

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

Tan,

Chen,

Kong

et al. 2023

Front. Aging Neurosci.

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Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

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Glutamatergic neurotransmission: A potential pharmacotherapeutic target for the treatment of cognitive disorders

Cited by 19 publications

References 310 publications

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms

IL-1β, the first piece to the puzzle of sepsis-related cognitive impairment?

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

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