Glutamate: Molecular Mechanisms and Signaling Pathway in Alzheimer’s Disease, a Potential Therapeutic Target DOI Creative Commons
Nidhi Puranik, Minseok Song

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5744 - 5744

Published: Dec. 5, 2024

Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays role transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations glutamatergic signaling pathway are now accepted as a element Alzheimer's disease (AD) pathophysiology. One of most prevalent types dementia older adults AD, progressive neurodegenerative illness brought on by persistent decline cognitive function. Since AD has been shown to be multifactorial, variety pharmaceutical targets may used treat condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists acetylcholinesterase inhibitors (AChEIs) two drug classes that Food Drug Administration authorized for treatment AD. The AChEIs approved galantamine, donepezil, rivastigmine. However, memantine only non-competitive NMDAR antagonist This review aims outline involvement glutamate (GLU) at molecular level pathways associated with demonstrate target therapeutic potential its receptor. We will also consider opinion leading authorities working this area, drawback existing strategies, direction further investigation.

Language: Английский

Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders DOI

Manzar Khan,

Divya Choudhary,

Sidharth Mehan

et al.

Neuropeptides, Journal Year: 2025, Volume and Issue: 111, P. 102516 - 102516

Published: March 12, 2025

Language: Английский

Citations

0
Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated Implications for Health and Disease DOI Creative Commons

Yuechang Wang,

Yonggang Zhang, Wei Wang

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 210 - 210

Published: March 20, 2025

Tryptophan is an essential amino acid critical for human health. It plays a pivotal role in numerous physiological and biochemical processes through its metabolism. The kynurenine (KYN) pathway serves as the principal metabolic route tryptophan, producing bioactive metabolites, including KYN, quinolinic acid, 3-hydroxykynurenine. Numerous studies are actively investigating relationship between tryptophan metabolism functions. These highlighting interactions among metabolites that may exert synergistic or antagonistic effects, such neuroprotective neurotoxic, pro-oxidative antioxidant activities. Minor disruptions homeostasis of these can result immune dysregulation, contributing to spectrum diseases. diseases include neurological disorders, mental illnesses, cardiovascular conditions, autoimmune diseases, chronic kidney disease. Therefore, understanding roles KYN elucidating contribution health regulation. present review emphasizes their mechanisms disease development, aiming establish theoretical basis leveraging dietary nutrients enhance

Language: Английский

Citations

0
Lamin A/C regulates cerebellar granule cell maturation DOI Creative Commons

Laura Vilardo,

Ingrid Cifola, Marta Nardella

et al.

Cell Biology and Toxicology, Journal Year: 2025, Volume and Issue: 41(1)

Published: April 5, 2025

Abstract Lamin A/C is a nuclear type V intermediate filament protein part of the meshwork structure underlying inner membrane (nuclear lamina), which plays numerous roles, including maintenance shape, heterochromatin organization, and transcriptional regulation. Our group has demonstrated role in different pathophysiological conditions. Here, we investigated for first time how affects neuronal maturation rat cerebellar granule cells (GCs). Primary GCs where silenced Lmna gene constituted our key model; this provided rather homogeneous cellular system showing population vitro. We then validated findings another vivo murine model with knock-out an vitro human silencing LMNA gene. observed across three models that down-regulation neurons by protecting from glutamate-evoked excitotoxicity correlates inhibition calcium influxes pro-inflammatory cytokine pathways. Consistent previous group, study corroborates neural development opens new significant implications better comprehension mechanisms involved neurodegenerative diseases, changes envelope are linked to neuroinflammatory processes damage.

Language: Английский

Citations

0
Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms DOI Creative Commons

Sameera Khan,

Nargis Bano,

Shakir Ahamad

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology mitochondrial involves multitude factors that remain elusive. This review centers on elucidating role(s) excitotoxicity, oxytosis/ferroptosis and neurodegeneration within context bioenergetics, biogenesis, mitophagy oxidative stress explores their intricate interplay pathogenesis diseases. effective coordination turnover processes, notably is assumed to be critically important for cellular resilience longevity. However, age-associated decrease impedes elimination dysfunctional mitochondria, consequently impairing biogenesis. deleterious cascade results accumulation damaged mitochondria deterioration functions. Both excitotoxicity have been demonstrated contribute significantly pathophysiology including Alzheimer's disease (AD), Parkinson's (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) Multiple (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates events involving calcium dysregulation, energy depletion, intricately linked dysfunction. Furthermore, emerging concepts surrounding underscore importance iron-dependent lipid peroxidation engagement neurodegeneration. not only discusses individual contributions ferroptosis but also emphasizes convergence with dysfunction, key driver Understanding crosstalk between oxytosis/ferroptosis, holds potential pave way mitochondrion-targeted therapeutic strategies. Such strategies, focus mitophagy, stress, emerge as promising avenues intervention.

Language: Английский

Citations

3
Bridging the Gap: Prenatal Nutrition, Myelination, and Schizophrenia Etiopathogenesis DOI
Minerva Ortiz‐Valladares, Óscar González-Pérez, Ricardo Pedraza‐Medina

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 558, P. 58 - 69

Published: Aug. 17, 2024

Language: Английский

Citations

2
Glutamate: Molecular Mechanisms and Signaling Pathway in Alzheimer’s Disease, a Potential Therapeutic Target DOI Creative Commons
Nidhi Puranik, Minseok Song

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5744 - 5744

Published: Dec. 5, 2024

Gamma-glutamate is an important excitatory neurotransmitter in the central nervous system (CNS), which plays role transmitting synapses, plasticity, and other brain activities. Nevertheless, alterations glutamatergic signaling pathway are now accepted as a element Alzheimer's disease (AD) pathophysiology. One of most prevalent types dementia older adults AD, progressive neurodegenerative illness brought on by persistent decline cognitive function. Since AD has been shown to be multifactorial, variety pharmaceutical targets may used treat condition. N-methyl-D-aspartic acid receptor (NMDAR) antagonists acetylcholinesterase inhibitors (AChEIs) two drug classes that Food Drug Administration authorized for treatment AD. The AChEIs approved galantamine, donepezil, rivastigmine. However, memantine only non-competitive NMDAR antagonist This review aims outline involvement glutamate (GLU) at molecular level pathways associated with demonstrate target therapeutic potential its receptor. We will also consider opinion leading authorities working this area, drawback existing strategies, direction further investigation.

Language: Английский

Citations

2