Year-end Sale % OFF 
Abstract
Alzheimer’s disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Glutamate is a nonessential amino acid and the major excitatory neurotransmitter synthesized from glucose. Alterations in cerebral glucose and glutamate levels precede the deposition of Aβ plaques. In the brain, over 40% of neuronal synapses are glutamatergic and disturbances in glutamatergic function have been implicated in pathophysiology of AD. Nevertheless, targeting the glutamatergic system seems to be a promising strategy to develop novel, improved therapeutics for AD. Here, we review data supporting the involvement of the glutamatergic system in AD pathophysiology as well as the efficacy of glutamatergic agents in this neurodegenerative disorder. We also discuss exciting new prospects for the development of improved therapeutics for this devastating disorder.
Highlights
Alzheimer’s disease (AD) is the most common and prevalent neurodegenerative disease with memory dysfunction and cognitive impairment, affecting nearly 46.8 million people worldwide, as reported by the World Health Organisation
Loss of EAAT2 function increases the activity of insulin-degrading enzymes in the liver, suggesting that the loss of EAATs causes insulin/protein kinase B signaling abnormalities in AD [83]. These findings suggest that EAAT2 loss/dysfunction associated with AD pathology and EAAT2 could be used as a therapeutic target for neuroprotection in glutamate-mediated excitotoxicity
Glutamate seems to play major roles in part because of its abundance in brain tissue and in part because it is at the crossroad of multiple metabolic pathways
Summary
Alzheimer’s disease (AD) is the most common and prevalent neurodegenerative disease with memory dysfunction and cognitive impairment, affecting nearly 46.8 million people worldwide, as reported by the World Health Organisation. HMW oligomers can dissociate into LMW species impairing synaptic functions [14] and in contrast, dissociation of Aβ oligomers into monomers in vivo could reduce Aβ pathology and synaptotoxicity [15]. Accumulation of Aβ plaques in synapse and the infiltration of tau into dendritic spines reduce excitatory glutamatergic synaptic transmission leading to cognitive impairments [28]. In the central nervous system (CNS), glutamate is the primary excitatory neurotransmitter acting on both ionotropic and metabotropic receptors It is at the crossroad between multiple metabolic pathways and plays an important role in the functions of learning and memory. The pathological accumulation of glutamate can induce neurotoxicity due to time-related exposure, over-stimulating the post-synaptic response causing an increase in the entry of Ca2+ into neurons [31]. The present review will extensively cover recent findings on the dysregulation of glutamatergic signaling in AD and will highlight the molecular mechanisms through which the modulation of glutamatergic receptors might exert beneficial effects in AD treatment
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
