Glimepiride protects neurons against amyloid-β-induced synapse damage

Osborne, Craig; West, Ewan; Nolan, William; McHale-Owen, Harriet; Williams, Alun; Bate, Clive

doi:10.1016/j.neuropharm.2015.09.030

Cited by 37 publications

(23 citation statements)

References 61 publications

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“…Blocking PrP function by anti-PrP reduces Aβ-mediated LTP impairments (Barry et al, 2011; Lauren et al, 2009). The compound glimepiride, a sulphonylurea approved for the treatment of diabetes mellitus, can reduce surface level of PrP by increased releasing of soluble PrP from neurons and may protect against Aβ-induced synapse damage by reducing Aβ-Prp interaction occurred within membrane micro-environments (Osborne et al, 2016). Intriguingly, others have failed to replicate the role of PrP in Aβ-induced synaptic depression, reduction in spine density, or blockade of LTP, regardless of whether PrP was overexpressed or ablated (Balducci et al, 2010; Calella et al, 2010; Kessels et al, 2010), arguing against a critical role of PrP as a coupling receptor.…”

Section: Aβ and Synaptic Functionsmentioning

confidence: 99%

Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease

Yan

Fan

Zhou

et al. 2016

Neuroscience & Biobehavioral Reviews

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Over the past two decades, many studies have identified significant contributions of toxic β-amyloid peptides (Aβ) to the etiology of Alzheimer’s disease (AD), which is the most common age-dependent neurodegenerative disease. AD is also recognized as a disease of synaptic failure. Aβ, generated by sequential proteolytic cleavages of amyloid precursor protein (APP) by BACE1 and γ-secretase, is one of major culprits that cause this failure. In this review, we summarize current findings on how BACE1-cleaved APP products impact learning and memory through proteins localized on glutamatergic, GABAergic, and dopaminergic synapses. Considering the broad effects of Aβ on all three types of synapses, BACE1 inhibition emerges as a practical approach for ameliorating Aβ-mediated synaptic dysfunctions. Since BACE1 inhibitory drugs are currently in clinical trials, this review also discusses potential complications arising from BACE1 inhibition. We emphasize that the benefits of BACE1 inhibitory drugs will outweigh the concerns.

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Section: Aβ and Synaptic Functionsmentioning

confidence: 99%

Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease

Yan

Fan

Zhou

et al. 2016

Neuroscience & Biobehavioral Reviews

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“…Following treatment, a reduction in Aβ induced synapse damage was observed [92]. Selectively inhibiting GPI-PLC reversed the protective effect of glimepiride, supporting the hypothesis that protective effect of glimepiride is due to activation of GPI-PLC [92]. Other studies have shown that glimepiride may exert its neuroprotective effect by serving as an agonist of PPAR-γ [93].…”

Section: Sulphonylureamentioning

confidence: 61%

“…In vitro neurons were damaged by Aβ before being treated with glimeperide. Following treatment, a reduction in Aβ induced synapse damage was observed [92]. Selectively inhibiting GPI-PLC reversed the protective effect of glimepiride, supporting the hypothesis that protective effect of glimepiride is due to activation of GPI-PLC [92].…”

Section: Sulphonylureamentioning

confidence: 63%

“…We found only one study evaluating the association between sulphonylureas and PD (described above) that showed an increased the risk of PD in diabetics taking sulphonylureas [83]. However, it has been demonstrated that glimepiride, but not glipizide, confers a neuroprotective effect in AD [92]. It was hypothesised that the difference exists because glimepiride activates endogenous glycosylphosphatidylinositol-phospholipase C (GPI-PLC) while glipizide does not.…”

Section: Sulphonylureamentioning

confidence: 99%

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Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

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Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Conclusion:Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

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“…+ PQT (10 mg/kg, i.p., in normal saline; twice per week for 3 weeks) . Dosages and route of drug administration were selected based on our preliminary findings as well as previous studies ), group 6: GPD (4 mg/kg, p.o. ).…”

Section: Methodsmentioning

confidence: 99%

Glimepiride prevents paraquat‐induced Parkinsonism in mice: involvement of oxidative stress and neuroinflammation

Ishola

Akataobi

Alade

et al. 2018

Fundamemntal Clinical Pharma

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There is a growing number of epidemiological and molecular studies which suggest that diabetes is associated with an increased risk of Parkinson's disease (PD). Hence, in this study, the effect of glimepiride (GPD), a sulphonylurea (antidiabetic) on paraquat (PQT)‐induced Parkinsonism was evaluated in mice. Thirty‐six mice were randomly divided into six groups (n = 6) and treated orally for 21 consecutive days as follows: Group 1: vehicle (10 mL/kg), Group 2: PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 3–5: GPD (1, 2 or 4 mg/kg) + PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 6: GPD (4 mg/kg, p.o.). The effects of the treatment on motor coordination were evaluated using the rotarod performance, bar and open field tests while working memory was assayed using Y‐maze test. Paraquat injection induced significant decrease in falling time, number of crosses and percentage alternation behaviour with a concomitant increase in the duration of cataleptic behaviour in the rotarod, open field, Y‐maze and bar tests, respectively, which was ameliorated by GPD treatment. PQT also increased lipid peroxidation, peroxynitrite and TNF‐α generations as well as deficit in superoxide dismutase and GSH activities in the midbrain. PQT‐induced oxidative stress and neuroinflammation was attenuated by GPD treatment. Findings from this study showed that GPD prevents PQT‐induced motor dysfunction, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of pro‐inflammatory cytokine release. Thus, GPD could be a potential adjunct in the management of Parkinsonism.

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Glimepiride protects neurons against amyloid-β-induced synapse damage

Cited by 37 publications

References 61 publications

Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease

Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease

Parkinson';s Disease, Diabetes and Cognitive Impairment

Glimepiride prevents paraquat‐induced Parkinsonism in mice: involvement of oxidative stress and neuroinflammation

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