Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: Targets for disease modification?

Bassil, Fares; Fernagut, Pierre‐Olivier; Bézard, Erwan; Meissner, Wassilios G.

doi:10.1016/j.pneurobio.2014.02.005

Cited by 193 publications

(167 citation statements)

References 294 publications

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“…In this regard, several clinical trials (30,31) aimed at exploring the effects of GLP-1R agonists on preventing the development of Alzheimer disease are in progress.…”

Section: Discussionmentioning

confidence: 99%

Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes

et al. 2015

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Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Since glucagonlike peptide 1 (GLP-1) exerts neuroprotective effects in the central nervous system and the retina is ontogenically a brain-derived tissue, the aims of the current study were as follows: 1) to examine the expression and content of GLP-1 receptor (GLP-1R) in human and db/db mice retinas; 2) to determine the retinal neuroprotective effects of systemic and topical administration (eye drops) of GLP-1R agonists in db/db mice; and 3) to examine the underlying neuroprotective mechanisms. We have found abundant expression of GLP-1R in the human retina and retinas from db/db mice. Moreover, we have demonstrated that systemic administration of a GLP-1R agonist (liraglutide) prevents retinal neurodegeneration (glial activation, neural apoptosis, and electroretinographical abnormalities). This effect can be attributed to a significant reduction of extracellular glutamate and an increase of prosurvival signaling pathways. We have found a similar neuroprotective effect using topical administration of native GLP-1 and several GLP-1R agonists (liraglutide, lixisenatide, and exenatide). Notably, this neuroprotective action was observed without any reduction in blood glucose levels. These results suggest that GLP-1R activation itself prevents retinal neurodegeneration. Our results should open up a new approach in the treatment of the early stages of DR.

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“…In this regard, several clinical trials (30,31) aimed at exploring the effects of GLP-1R agonists on preventing the development of Alzheimer disease are in progress.…”

Section: Discussionmentioning

confidence: 99%

Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes

et al. 2015

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“…There is a certain degree of cross-talk between insulin, IGF-1, and their receptors (51). Insulin/IGF-1 pathways may have a role in the regulation of longevity (54), and dysfunction of these pathways may contribute to the progressive loss of neurons in Alzheimer disease and Parkinson disease (55).…”

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confidence: 99%

Insulin and Insulin-like Growth Factor 1 (IGF-1) Modulate Cytoplasmic Glucose and Glycogen Levels but Not Glucose Transport across the Membrane in Astrocytes

Muhič

Vardjan

Chowdhury

et al. 2015

Journal of Biological Chemistry

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Background: Astrocytes contain glycogen, an energy buffer in the brain. Results: Stimulation with insulin and IGF-1 decreases cytosolic glucose concentration in astrocytes without affecting glucose entry across the astrocyte plasma membrane. Conclusion: Insulin and IGF-1 boost the process of glycogen formation. Significance: This is the first high temporal resolution measurement of the decrease of glucose levels in astrocytes resulting from insulin and IGF-1 stimulation.

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“…Insulin/IGF-1 (Insulin-like growth factor 1) signalling has long been implicated in modulating neurodegenerative diseases [180]. In this regard, studies show increasing IGF-1 levels in SMA mice can have many phenotypic benefits including increased muscle size, motor function, lifespan, NMJ innervation and motor neurone number [56,181].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Spinal muscular atrophy: Factors that modulate motor neurone vulnerability

Simpson

Highley

et al. 2017

Neurobiology of Disease

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Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets. Keywords:Selective vulnerability, SMA, SMN, disease modifier, motor neurone disease ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T Highlights: Factors that influence vulnerability of motor neurons in SMA. SMA disease modification. Impact of surrounding cells on neuronal death. Precise molecular defects in SMA; mRNA splicing and miRNA interactions. Cytoskeletal stability and axonal transport effects.

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Insulin, IGF-1 and GLP-1 signaling in neurodegenerative disorders: Targets for disease modification?

Cited by 193 publications

References 294 publications

Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes

Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes

Insulin and Insulin-like Growth Factor 1 (IGF-1) Modulate Cytoplasmic Glucose and Glycogen Levels but Not Glucose Transport across the Membrane in Astrocytes

Spinal muscular atrophy: Factors that modulate motor neurone vulnerability

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