Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms

Table 1 Research targeted astrocyte and its signaling pathway, protein kinases, receptors, and channels for diabetic neuropathy treatment

Name of treatment	Target treatment	Target cells	Mediator/cells, receptor regulated via activation	Molecular mechanisms	Ref.
MK-801	Protein kinase-MAPKs	Microglia, neuron	NMDA receptor	Protein kinases	Daulhac et al[91], 2006
PARP inhibitor, 1,5-isoquinolinediol	Enzyme- poly (ADP-ribose) polymerase (PPAR)	Microglia, neuron, astrocytes	Isoprostane, 8-hydroxy-2′-deoxyguanosine excretion, 4-hydroxynonenal adduct accumulation	Enzymes	Lupachyk et al[92], 2011
MK-801	Receptor-NMDA receptor	Neuron, astrocytes	ERK1/2, NMDA receptor, nNOS, iNOS	Receptor-related mechanisms	Dauch et al[93], 2012
U0126	Extracellular signal-regulated protein kinase	Neuron, astrocytes	p-ERK, Iba1, GFAP, NeuN	Protein kinases	Xu et al[94], 2014
levetiracetam	Channels-calcium channel	Microglia, astrocytes	CD11b and GFAP expression	Ion channels	Reda et al[95], 2016
Lycopene	Gap junction- Connexin43	Astrocytes	GFAP and TNF-α expression	Gap junctions	Zhang et al[96], 2016
Dexmedetomidine	Receptor-α2 adrenergic agonist	Astrocytes, microglial	Iba1, GFAP, IL-1β, TNF-α, glutamate	Receptor-related mechanisms	Lu et al[97], 2017
Mesenchymal stem/stromal cells	Cytokines-IL-1β, and TNF-α	Astrocytes, microglia	Iba1, GFAP, catalase, glutathione peroxidase, superoxide dismutase, Nrf2, MDA, IL-1β, TNF-α	Cytokines signaling	Evangelista et al[98], 2018
Duloxetine	Receptor-Serotonin noradrenaline reuptake inhibitor	Astrocytes, microglia	CD11, GFAP, sciatic mRNA expression of NGF	Receptor-related mechanisms	Tawfik et al[99], 2018
Dexmedetomidine	Signaling pathway-Wnt 10a/β-Catenin	Astrocytes	TNF-α, IL-1β, GFAP, Wnt 10a and β-catenin	Signaling pathways	Zhong et al[100], 2018
Ammoxetine	Receptor-Serotonin and norepinephrine reuptake inhibitors	Astrocytes, microglia	Iba1, GFAP, MAPKs, NF-κβ, IL-1β, TNF-α, IL-6	Receptor-related mechanisms	Zhang et al[101], 2018
Hydrogen sulfide donor GYY4137	Cytokines-proinflammatory mediators	Astrocytes, microglia	Iba1, GFAP, neuron, IL-1β, IL-6, TNF-α	Cytokines signaling	Shayea et al[102], 2020
Curcumin	Protein kinases-c-Jun N-terminal kinase	Astrocytes, neurons	p-JNK expression	Protein kinases	Park et al[103], 2021
Fluorocitrate	Selective inhibitor of astrocyte activation	Astrocytes	GFAP expression	Selective inhibitors	Liu et al[104], 2022
Semaglutide	GLP-1 receptor agonists	Astrocytes, microglia	HbA1c, AGEs, Iba1, GFAP, IL-1β, IL-6, TNF-α	GLP-1 receptor agonists	Lee et al[105], 2024

AGEs: Advanced glycation end products; GFAP: Glial fibrillary acidic protein; HbA1c: Glycated hemoglobin; IL-1β: Interleukin 1 beta; IL-6: Interleukin 6; TNF-α: Tumor necrosis factor alpha; iNOS: Inducible nitric oxide synthase; nNOS: Neuronal nitric oxide synthase; NF-κβ: Nuclear factor kappa β; NMDA: N-methyl D-aspartate; ERK: Extracellular signal-regulated kinase; Iba1: Ionized calcium-binding adaptor molecule 1; NeuN: Neuronal nuclei; CD11b: Cluster of differentiation 11b; Nrf2: Nuclear factor erythroid 2–related factor 2; MDA: Malondialdehyde; NGF: Nerve growth factor; MAPKs: Mitogen-activated protein kinases; JNK: C-Jun N-terminal kinase.