Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer's disease and diabetes

Bak, Ann Mosegaard; Egefjord, Lærke; Gejl, Michael; Steffensen, Charlotte; Stecher, Chalotte Willemann; Smidt, Kamille; Brock, Birgitte; Rungby, Jørgen

doi:10.1517/14728222.2011.600691

Cited by 31 publications

(19 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The efficacy of GLP-1 receptor signaling observed here is in line with literature describing GLP-1 and Ex-4 brain entry (Kastin and Akerstrom, 2003), and GLP-1 receptor-mediated actions in various CNS neurological conditions (for review see, Holsher 2010; Holst et al 2011; Bak et al 2011; Salcedo et al 2012). The utility of GLP-1 receptor stimulation in diverse disease states such as AD, PD, HD, ALS, stroke and peripheral neuropathy signifies commonalities in what are likely to be the latter stages of neuronal cell death observed in these conditions (Li et al 2009, 2010, 2012; Martin et al 2009; Perry et al 2007).…”

Section: Discussionsupporting

confidence: 88%

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

Tweedie

Rachmany

Rubovitch

et al. 2013

Experimental Neurology

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer’s disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury.

show abstract

Section: Discussionsupporting

confidence: 88%

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

Tweedie

Rachmany

Rubovitch

et al. 2013

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…Moreover, incretin hormones also show additional properties, specifically neurotrophic activity and protective effect, in T2DM-associated neurodegeneration (Hamilton et al, 2011;Salcedo et al, 2012). Recently, studies investigating the effects of incretin-based therapy on neurodegenerative diseases have been published, which show very promising results and may indicate an alternative approach for treating these patients (Perry and Greig, 2004;Harkavyi and Whitton, 2010;Li et al, 2010b;Bak et al, 2011;Mossello et al, 2011;Sakurai, 2011;Luchsinger, 2012;Salcedo et al, 2012;Holscher, 2014a,c;Ji et al, 2016a). In this review, we primarily discuss the progress of ongoing research on the protection of incretin-based therapy against neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Hölscher

2016

Reviews in the Neurosciences

View full text Add to dashboard Cite

AbstractIncretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Due to their promising action on insulinotropic secretion and improving insulin resistance (IR), incretin-based therapies have become a new class of antidiabetic agents for the treatment of type 2 diabetes mellitus (T2DM). Recently, the links between neurodegenerative diseases and T2DM have been identified in a number of studies, which suggested that shared mechanisms, such as insulin dysregulation or IR, may underlie these conditions. Therefore, the effects of incretins in neurodegenerative diseases have been extensively investigated. Protease-resistant long-lasting GLP-1 mimetics such as lixisenatide, liraglutide, and exenatide not only have demonstrated promising effects for treating neurodegenerative diseases in preclinical studies but also have shown first positive results in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients in clinical trials. Furthermore, the effects of other related incretin-based therapies such as GIP agonists, dipeptidyl peptidase-IV (DPP-IV) inhibitors, oxyntomodulin (OXM), dual GLP-1/GIP, and triple GLP-1/GIP/glucagon receptor agonists on neurodegenerative diseases have been tested in preclinical studies. Incretin-based therapies are a promising approach for treating neurodegenerative diseases.

show abstract

“…Coincidentally, a hormone called glucagon-like peptide 1 (GLP-1) has recently been tested with very promising results as a possible treatment to AD [8][9][10]. This coincides with the above logic regarding glucagon related substances possibly playing a role in downgrading cortisol levels and possibly having a positive influence in treatment of Alzheimer's Disease.…”

Section: Commentarymentioning

confidence: 72%

Rethinking Glucose Role in Alzheimer's Disease Based on the Disease Incidence in Diabetes Type 2 Patients

Gelbard¹

2017

J Gerontol Geriatr Res

View full text Add to dashboard Cite

Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer's disease and diabetes

Abstract: A convincing amount of evidence has shown a beneficial effect of GLP-1 agonist treatment on cognitive function, memory and learning in experimental models of AD. GLP-1 analogues may therefore be the new therapeutic agent of choice for intervention in AD.

Cited by 31 publications

References 85 publications

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Rethinking Glucose Role in Alzheimer's Disease Based on the Disease Incidence in Diabetes Type 2 Patients

Contact Info

Product

Resources

About