Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1–42)-induced cognitive deficit rats

Garabadu, Debapriya; Verma, Jaya

doi:10.1016/j.neuint.2019.04.006

Cited by 49 publications

(32 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AD is a major cause of dementia which is a common disease among the elderly, starting with an irreversible decline in episodic memory and then a more general decline in overall cognitive ability [ 2 , 3 ]. AD is characterized by disorientation and gradual deterioration of memory and intelligence [ 4 , 5 ]. About 12% of people over 65 are affected.…”

Section: Introductionmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer’s disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

show abstract

Section: Introductionmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…First alterations of cerebral glucose metabolism in the Aβ1-42 model were recorded 2 weeks following the treatment when decreased levels of glucose were detected in hippocampal neurons and increased concentration was observed in the cerebrospinal fluid (Table 1) (Pearson-Leary et al 2012). The same study found no changes in GLUT1 and GLUT3 expression in the hippocampus but translocation of the insulin-sensitive GLUT4 transporter from the intracellular compartment to the membrane was decreased (Pearson-Leary et al 2012), as reported also by Garabadu and Verma (2019).…”

Section: Time Course Of the Appearance Of Insulin Signalling Dysfunctmentioning

confidence: 71%

“…Research on insulin signalling dysfunction in the brain of the Aβ 1-42 model is modest, revealing decreased phosphorylation of AKT in the rat hippocampus 2 weeks following Aβ 1-42 treatment (Table 1) (Pearson-Leary et al 2012;Garabadu and Verma 2019).…”

Section: Time Course Of the Appearance Of Insulin Signalling Dysfunctmentioning

confidence: 99%

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

et al. 2020

View full text Add to dashboard Cite

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and coexpression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/ PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

“…It was proved that oleuropein could effectively alleviate learning and memory impairment in morphine-treated rats by inhibiting neuronal apoptosis and oxidative stress [44]. The MWM test was also pervasively used to evaluate cognition impairments, which exist in various AD models [45,46,47]. The experimental system mainly contains a water maze device, and an automatic image acquisition and software analysis system [48].…”

Section: Methodsmentioning

confidence: 99%

Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry

et al. 2019

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disorder that damages health and welfare of the elderly, and there has been no effective therapy for AD until now. It has been proved that tanshinone IIA (tan IIA) could alleviate pathological symptoms of AD via improving non-amyloidogenic cleavage of amyloid precursor protein, decreasing the accumulations of p-tau and amyloid-β1–42 (Aβ1–42), and so forth. However, the further biochemical mechanisms of tan IIA are not clear. The experiment was undertaken to explore metabolites of tan IIA in AD rats induced by microinjecting Aβ1-42 in the CA1 region of hippocampus. AD rats were orally administrated with tan IIA at 100 mg/kg weight, and plasma, urine, faeces, kidney, liver and brain were then collected for metabolites analysis by UHPLC-Q-Exactive Qrbitrap mass spectrometry. Consequently, a total of 37 metabolites were positively or putatively identified on the basis of mass fragmentation behavior, accurate mass measurements and retention times. As a result, methylation, hydroxylation, dehydration, decarbonylation, reduction reaction, glucuronidation, glycine linking and their composite reactions were characterized to illuminate metabolic pathways of tan IIA in vivo. Several metabolites presented differences in the distribution of tan IIA between the sham control and the AD model group. Overall, these results provided valuable references for research on metabolites of tan IIA in vivo and its probable active structure for exerting neuroprotection.

show abstract

Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1–42)-induced cognitive deficit rats

Cited by 49 publications

References 57 publications

Role of Cholinergic Signaling in Alzheimer’s Disease

Role of Cholinergic Signaling in Alzheimer’s Disease

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

Rapid Identification of Tanshinone IIA Metabolites in an Amyloid-β1-42 Induced Alzherimer’s Disease Rat Model using UHPLC-Q-Exactive Qrbitrap Mass Spectrometry

Contact Info

Product

Resources

About