Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats

Cai, Hong-Yan; Hölscher, Christian; Yue, Xing-Hua; Zhang, S.-X.; Wang, X.-H.; Qiao, Feng; Yang, Weiren; Qi, Jin-Shun

doi:10.1016/j.neuroscience.2014.02.022

Cited by 77 publications

(64 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2014, Cai et al reported for the first time the effects of lixisenatide on Aβ-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms [215]. These researchers found that lixisenatide (5 nmol/μl, ICV) treatment: (i) effectively prevented Aβ(25–35)-induced cognitive impairments; and (ii) inhibited Aβ(25–35) injection-induced activation of GSK3β, with a significant increase in the phosphorylation of Ser9 and a significant decrease in the phosphorylation of Tyr216 [215]. …”

Section: Oxidative Stress and Insulin Resistance: Therapeutic Apprmentioning

confidence: 99%

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Butterfield

Domenico

Barone

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

319

244

View full text Add to dashboard Cite

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field.

show abstract

Section: Oxidative Stress and Insulin Resistance: Therapeutic Apprmentioning

confidence: 99%

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Butterfield

Domenico

Barone

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

319

244

View full text Add to dashboard Cite

show abstract

“…The most prominent clinical symptom of Alzheimer’s disease (AD) is progressive cognitive decline [1]. The characteristic loss of episodic memories is an area under focused investigation and heavily dependent on amyloid-β (Aβ) plaques and neurofibrillary tau tangles (NFTs) [2].…”

Section: Introductionmentioning

confidence: 99%

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Lucke‐Wold

Turner

Logsdon

et al. 2014

JAD

View full text Add to dashboard Cite

Ischemic stroke and Alzheimer’s disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.

show abstract

“…Lixisenatide is based on exendin-4 (1–39) molecule and has a modified C-terminal with six additional lysine residues that confers a fourfold higher affinity to the GLP-1R than the human GLP-1, together with a half-life of about 3 h (139, 140). Similar to liraglutide, lixisenatide also crosses the BBB into CNS, whereby it has been shown to exert strong neurogenic effects in an AD rodent model (124, 141) (Figure 1), as well as to prevent Aβ-related impaired synaptic plasticity, hippocampal LTP, and spatial learning memory in a PI3K/Akt/GSK-3β-mediated pathway (142). Despite such potent brain protective effects, further in vivo and clinical research aiming at the treatment of neurodegenerative diseases with lixisenatide are needed.…”

Section: Introductionmentioning

confidence: 99%

Insulin as a Bridge between Type 2 Diabetes and Alzheimer Disease â€“ How Anti-Diabetics Could be a Solution for Dementia

Sebastião¹,

Candeias

Santos

et al. 2014

Front. Endocrinol.

View full text Add to dashboard Cite

Type 2 diabetes (T2D) and Alzheimer disease (AD) are two major health issues nowadays. T2D is an ever increasing epidemic, affecting millions of elderly people worldwide, with major repercussions in the patients’ daily life. This is mostly due to its chronic complications that may affect brain and constitutes a risk factor for AD. T2D principal hallmark is insulin resistance which also occurs in AD, rendering both pathologies more than mere unrelated diseases. This hypothesis has been reinforced in the recent years, with a high number of studies highlighting the existence of several common molecular links. As such, it is not surprising that AD has been considered as the “type 3 diabetes” or a “brain-specific T2D,” supporting the idea that a beneficial therapeutic strategy against T2D might be also beneficial against AD. Herewith, we aim to review some of the recent developments on the common features between T2D and AD, namely on insulin signaling and its participation in the regulation of amyloid β (Aβ) plaque and neurofibrillary tangle formation (the two major neuropathological hallmarks of AD). We also critically analyze the promising field that some anti-T2D drugs may protect against dementia and AD, with a special emphasis on the novel incretin/glucagon-like peptide-1 receptor agonists.

show abstract

Lixisenatide rescues spatial memory and synaptic plasticity from amyloid β protein-induced impairments in rats

Cited by 77 publications

References 64 publications

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

Insulin as a Bridge between Type 2 Diabetes and Alzheimer Disease â€“ How Anti-Diabetics Could be a Solution for Dementia

Contact Info

Product

Resources

About