Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model

Zhang, Yanfang; Chen, YiMei; Li, Lin; Hölscher, Christian

doi:10.1016/j.bbr.2015.07.021

Cited by 42 publications

(28 citation statements)

References 45 publications

(51 reference statements)

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“…Furthermore, two previous studies showed good protection of MPTP treated mice using the GLP-1 agonist exendin-4 (Kim et al, 2009; Li et al, 2009). We also tested the newer GLP-1 receptor agonists liraglutide, lixisenatide and (Val8)GLP-1gluPAL in this model with good neuroprotective effects (Liu et al, 2015;Zhang et al, 2015). Exendin-4 also has been tested in a pilot study in Parkinson's patients with promising first results (Aviles-Olmos et al, 2013.…”

Section: Discussionmentioning

confidence: 97%

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease

Liu

Jalewa

et al. 2015

European Journal of Pharmacology

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Section: Discussionmentioning

confidence: 97%

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease

Liu

Jalewa

et al. 2015

European Journal of Pharmacology

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“…The activation of GLP-1 receptors that activate cell growth signaling pathways may be the mechanism by which geniposide exerted the neuroprotective effects in our study. We have previously shown that GLP-1 receptor agonists show neuroprotective effects in the MPTP mouse model (Liu et al, 2015a;Zhang et al, 2015). However, further research in the mechanisms of action of geniposide is required.…”

Section: Discussionmentioning

confidence: 98%

Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease

Chen

Zhang

et al. 2015

European Journal of Pharmacology

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“…Our recent research has demonstrated neuroprotective effects of Val(8)GLP‐1‐GluPal in the MPTP PD mouse model (Zhang et al . ). Oxyntomodulin is a GLP‐1 and glucagon receptor dual agonist (Pocai ).…”

mentioning

confidence: 97%

“…Val(8)GLP-1-GluPal is a new GLP-1 analogue that has longer biological half-life (Lennox et al 2013). Our recent research has demonstrated neuroprotective effects of Val(8)GLP-1-GluPal in the MPTP PD mouse model (Zhang et al 2015). Oxyntomodulin is a GLP-1 and glucagon receptor dual agonist (Pocai 2012).…”

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confidence: 99%

Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone inSH‐SY5Y cells

Jalewa

Sharma

Hölscher

2016

Journal of Neurochemistry

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Currently, there is no viable treatment available for Parkinson's disease (PD) that stops or reverses disease progression. Interestingly, studies testing the glucagon-like-peptide-1 (GLP-1) mimetic Exendin-4 have shown neuroprotective/neurorestorative properties in pre-clinical tests and in a pilot clinical study of PD. Incretin analogues were originally developed to treat type 2 diabetes and several are currently on the market. In this study, we tested novel incretin analogues on the dopaminergic SH-SY5Y neuroblastoma cells against a toxic mitochondrial complex I inhibitor, Rotenone. Here, we investigate for the first time the effects of six different incretin receptor agonists - Liraglutide, D-Ser2-Oxyntomodulin, a GLP-1/GIP Dual receptor agonist, dAla(2)-GIP-GluPal, Val(8)GLP-1-GluPal and exendin-4. Post-treatment with doses of 1, 10 or 100 nM of incretin analogues for 12 h increased the survival of SH-SY5Y cells treated with 1 μM Rotenone for 12 h. Furthermore, we studied the post-treatment effect of 100 nM incretin analogues against 1 μM Rotenone stress on apoptosis, mitochondrial stress and autophagy markers. We found significant protective effects of the analogues against Rotenone stress on cell survival and on mitochondrial and autophagy-associated markers. The novel GLP-1/GIP Dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. Using the Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, we further show that the neuroprotective effects are partially PI3K-independent. Our data suggest that the neuroprotective properties exhibited by incretin analogues against Rotenone stress involve enhanced autophagy, increased Akt-mediated cell survival and amelioration of mitochondrial dysfunction. These mechanisms can explain the neuroprotective effects of incretin analogues reported in clinical trials. GLP-1, GIP and dual incretin receptor agonists showed protective effects in SH-SY5Y cells treated with the stressor Rotenone. The novel GLP-1/GIP dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. The drugs protected the cells from rotenone-induced impairment in cell growth and Akt activation, mitochondrial damage, impairments of autophagy and apoptotic cell signalling. See paper for details.

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Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model

Cited by 42 publications

References 45 publications

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease

Neuroprotective effects of an oxyntomodulin analogue in the MPTP mouse model of Parkinson's disease

Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease

Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone inSH‐SY5Y cells

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