The GABA–Working Memory Relationship in Alzheimer’s Disease

Mandal, Pravat K.; Kansara, Krity; Dabas, Aroma

doi:10.3233/adr-170003

Cited by 23 publications

(20 citation statements)

References 25 publications

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“…In severe AD patients, GABA levels have been shown to be significantly reduced, which may be the cause of AD behavior and psychological symptoms (Calvo-Flores Guzmán et al, 2018). Increasing evidence supports the remodeling of GABAergic synapses in the AD brain, which may begin in the early stages of disease pathogenesis last through the entire course of AD (Mandal et al, 2017). Therefore, GABAergic synapses may become effective molecular targets for AD drug development and pharmacological treatment.…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Targets of Fingolimod (FTY720) Are Involved in Pathological Processes in the Frontal Cortex of Alzheimer's Disease Patients: A Network Pharmacology Study

Yin

Xue

Wang

et al. 2021

Front. Aging Neurosci.

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Background: The sphingosine-1-phosphate receptor (S1PR) modulator fingolimod (FTY720), which is commonly used as an immunomodulator in multiple sclerosis treatment, has recently been found to reduce pathological changes in the brain tissue of Alzheimer's disease (AD) animal models, but this has yet to be verified in human brain tissue. In this study, network pharmacology methods were applied to determine the potential pharmacological mechanisms of fingolimod in the frontal cortex of AD patients.Methods: The pharmacological macromolecular targets of fingolimod and fingolimod phosphate were downloaded from SwissTarget and DrugBank. Systematic intersection analysis of the expression profiles of brain frontal cortex tissues (423 AD tissues and 266 control tissues) was performed to obtain AD-associated fingolimod targets (F-ADGs). Immune cell infiltration analysis and a primary mouse cortical culture RNA-seq drug screen database were used to identify immune-related F-ADGs and cortex-related F-ADGs. Then, the expression values of F-ADGs were correlated with the disease severity score (MMSE score) of AD patients to identify severity-related F-ADGs. We also analyzed miRNA expression microarray data in the frontal cortex of AD patients associated with disease severity to obtain severity-related F-ADG-miRNAs.Results: A total of 188 F-ADGs were detected in the frontal cortices of AD patients and were enriched in biological processes such as synaptic signaling, inflammatory response, and response to oxygen-containing compounds. Eleven immune-related F-ADGs (like FPR1, BLNK.) and 17 cortex-related F-ADGs (like ALDH1L1, DUSP1.) were detected. Other F-ADGs, such as S1PR1 and GABBR2, although not classified into the above two categories, were still predicted by bioinformatics methods to play an important role in the development of AD. Two F-ADGs (GNAQ and MMP14) and 28 miRNAs (like miR- 323a-3p, miR-181a-5p.) were found to be associated with AD severity (MMSE 0-27 group). Fifteen F-ADGs (like ALDH1L1, FPR1, and IL6.) and 46 miRNAs (like miR-212-5p, miR-93-5p.) were found to be associated with mild or moderate dementia AD patients' severity (MMSE11-22 subgroup).Conclusions: Fingolimod may affect the brain frontal cortex function of AD patients in many different ways, such as affecting immune cell infiltration, nerve cell, or glial cell function, and synaptic function. miRNAs may also be involved. ALDH1L1, FPR1, S1PR1, and GABBR2 may be core drug targets.

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Section: Discussionmentioning

confidence: 99%

The Therapeutic Targets of Fingolimod (FTY720) Are Involved in Pathological Processes in the Frontal Cortex of Alzheimer's Disease Patients: A Network Pharmacology Study

Yin

Xue

Wang

et al. 2021

Front. Aging Neurosci.

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“…A main concern of these studies is that they quantified GABA from post-mortem tissues. Post-mortem studies usually measure GABA by examining the activity of its synthesizing enzyme glutamic acid decarboxylase (GAD), but GAD is easily affected by pre-mortem environments, which can affect the measurements [39]. As such, more research is needed to understand the contribution of GABA levels and transmission in AD.…”

Section: Dysfunction Of Cholinergic Neurotransmissionmentioning

confidence: 99%

Regulation of Melatonin and Neurotransmission in Alzheimer’s Disease

Roy

Tsui

et al. 2021

IJMS

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Alzheimer’s disease is a neurodegenerative disorder associated with age, and is characterized by pathological markers such as amyloid-beta plaques and neurofibrillary tangles. Symptoms of AD include cognitive impairments, anxiety and depression. It has also been shown that individuals with AD have impaired neurotransmission, which may result from the accumulation of amyloid plaques and neurofibrillary tangles. Preclinical studies showed that melatonin, a monoaminergic neurotransmitter released from the pineal gland, is able to ameliorate AD pathologies and restore cognitive impairments. Theoretically, inhibition of the pathological progression of AD by melatonin treatment should also restore the impaired neurotransmission. This review aims to explore the impact of AD on neurotransmission, and whether and how melatonin can enhance neurotransmission via improving AD pathology.

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“…Ukrainian scientists determined a correcting effect of carbacetam on the cognitive functions under conditions of experimental craniocerebral injury 13 . Considering the fact that GABA-ERGIC mechanisms play an important role in the pathogenesis of memory deterioration 14,15 , the study of therapeutic properties du carbacetam dans le test «en champ ouvert» étaient caractérisées par la diminution du temps de «l'immobilité», par l'augmentation de l'activité motrice ; dans le test du «reflexe conditionnel d'évitement passif» par l'augmentation de la période de latence de l'entré des rats dans une chambre obscure connectée au courant électrique. Conclusions.…”

Section: Introductionunclassified

Carbacetam effect on behavioral reactions in experimental Alzheimer’s disease

Kmet¹,

Зябліцев²,

Filipets³

et al. 2019

Arch Balk Med Union

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L'influence du carbacetam sur les réactions comportementales dans la maladie d'Alzheimer expérimentale Introduction. Compte tenu de l'efficacité insuffisante des traitements modernes, la recherche de nouveaux moyens de la thérapie pathogénique de la maladie d'Alzheimer est pertinente. Le but de l'étude est d'évaluer l'efficacité du nouveau modulateur original du système GABA-ERGIQUE du carbacetam en ce qui concerne la dynamique des modifications des indicateurs des réactions comportementales des rats atteints du modèle de la maladie d'Alzheimer. Matériaux et méthodes. Le modèle de la maladie d'Alzheimer a été créé par l'administration intra-abdominale pendant 27 jours de chlorhydrate de scopolamine (Sigma, USA) à une dose de 1 mg/kg. à partir du 28e jour de l'expérience ; le carbacetam a été administré par voie intra-péritonéale à une dose de 5 mg/ kg dans 1 ml de solution saline physiologique, une fois par jour pendant 14 jours. Résultats. Les réactions comportementales des rats atteints de la maladie d'Alzheimer après l'introduction

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The GABA–Working Memory Relationship in Alzheimer’s Disease

Cited by 23 publications

References 25 publications

The Therapeutic Targets of Fingolimod (FTY720) Are Involved in Pathological Processes in the Frontal Cortex of Alzheimer's Disease Patients: A Network Pharmacology Study

The Therapeutic Targets of Fingolimod (FTY720) Are Involved in Pathological Processes in the Frontal Cortex of Alzheimer's Disease Patients: A Network Pharmacology Study

Regulation of Melatonin and Neurotransmission in Alzheimer’s Disease

Carbacetam effect on behavioral reactions in experimental Alzheimer’s disease

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