Targeting mGluR group III for the treatment of neurodegenerative diseases

Rabeh, Nadia; Hajjar, Baraa; Maraka, Jude O.; Sammanasunathan, Ashwin F.; Khan, Mohammed; Alkhaaldi, Saif M.I.; Mansour, Samy; Almheiri, Rashed T.; Hamdan, Hamdan; Abd-Elrahman, Khaled S.

doi:10.1016/j.biopha.2023.115733

Cited by 6 publications

(1 citation statement)

References 208 publications

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“…Extending across the expansive neural network, these receptors initiate complex signaling cascade. Deciphering the unique signatures of their signaling is pivotal, as it holds the promise of unveiling targeted therapeutic strategies for a spectrum of neuropsychiatric and neurodegenerative diseases ( Ribeiro et al, 2010 ; Abd-Elrahman and Ferguson, 2021 ; Li et al, 2022 ; Rabeh et al, 2023 ).…”

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confidence: 99%

Editorial: Emerging insights in glutamate receptor signaling in psychiatric, neurodevelopmental, and neurodegenerative diseases

Abd-Elrahman,

Beaulieu,

Ferguson

2024

Front. Cell Dev. Biol.

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confidence: 99%

Editorial: Emerging insights in glutamate receptor signaling in psychiatric, neurodevelopmental, and neurodegenerative diseases

Abd-Elrahman,

Beaulieu,

Ferguson

2024

Front. Cell Dev. Biol.

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Interactions between metabotropic glutamate and CB1 receptors: implications for mood, cognition, and synaptic signaling based on data from mGluR and CB1R-targeting drugs

Stachowicz

2024

Pharmacol. Rep

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Metabotropic glutamate receptors (mGluRs) are part of the G protein-coupled receptors (GPCRs) family. They are coupled to Gαq (group I) or Gi/o (groups II and III) proteins, which result in the generation of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) or the inhibition of adenylyl cyclase, respectively. mGluRs have been implicated in anxiety, depression, learning, and synaptic plasticity. Similarly, CB1 cannabinoid receptors (CB1Rs), also GPCRs, play roles in cognitive function and mood regulation through Gαi/o–mediated inhibition of adenylyl cyclase. Both mGluRs and CB1Rs exhibit surface labeling and undergo endocytosis. Given the similar cellular distribution and mechanisms of action, this review complies with fundamental data on the potential interactions and mutual regulation of mGluRs and CB1Rs in the context of depression, anxiety, and cognition, providing pioneering insights into their interplay.

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Metabotropic glutamate receptors—guardians and gatekeepers in neonatal hypoxic-ischemic brain injury

Mielecki,

Bratek-Gerej,

Salińska

2024

Pharmacol. Rep

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Injury to the developing central nervous system resulting from perinatal hypoxia–ischemia (HI) is still a clinical challenge. The only approach currently available in clinical practice for severe cases of HI is therapeutic hypothermia, initiated shortly after birth and supported by medications to regulate blood pressure, control epileptic seizures, and dialysis to support kidney function. However, these treatments are not effective enough to significantly improve infant survival or prevent brain damage. The need to create a new effective therapy has focused attention on metabotropic glutamate receptors (mGluR), which control signaling pathways involved in HI-induced neurodegeneration. The complexity of mGluR actions, considering their localization and developmental changes, and the functions of each subtype in HI-evoked brain damage, combined with difficulties in the availability of safe and effective modulators, raises the question whether modulation of mGluRs with subtype-selective ligands can become a new treatment in neonatal HI. Addressing this question, this review presents the available information concerning the role of each of the eight receptor subtypes of the three mGluR groups (group I, II, and III). Data obtained from experiments performed on in vitro and in vivo neonatal HI models show the neuroprotective potential of group I mGluR antagonists, as well as group II and III agonists. The information collected in this work indicates that the neuroprotective effects of manipulating mGluR in experimental HI models, despite the need to create more safe and selective ligands for particular receptors, provide a chance to create new therapies for the sensitive brains of infants at risk.

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Targeting mGluR group III for the treatment of neurodegenerative diseases

Cited by 6 publications

References 208 publications

Editorial: Emerging insights in glutamate receptor signaling in psychiatric, neurodevelopmental, and neurodegenerative diseases

Editorial: Emerging insights in glutamate receptor signaling in psychiatric, neurodevelopmental, and neurodegenerative diseases

Interactions between metabotropic glutamate and CB1 receptors: implications for mood, cognition, and synaptic signaling based on data from mGluR and CB1R-targeting drugs

Metabotropic glutamate receptors—guardians and gatekeepers in neonatal hypoxic-ischemic brain injury

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