Apelin-13 attenuates motor impairments and prevents the changes in synaptic plasticity-related molecules in the striatum of Parkinsonism rats

Wang

et al. 2020

IJMS

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain–gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPKα inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.

Section: Discussionmentioning

confidence: 99%

Apelin-13 Protects Dopaminergic Neurons against Rotenone—Induced Neurotoxicity through the AMPK/mTOR/ULK-1 Mediated Autophagy Activation

Wang

et al. 2020

IJMS

“…animal study adult Wistar rats were divided into seven treatment groups, with seven rats in each group neurexin 1 expression is decreased in the striatum of 6-OHDA-induced rats [112] experimental groups had 6-OHDA brain injections with or without different concentrations of apelin-13…”

Section: Nrxn3mentioning

confidence: 99%

Emerging evidence implicating a role for neurexins in neurodegenerative and neuropsychiatric disorders

et al. 2021

Synaptopathies are brain disorders characterized by dysfunctional synapses, which are specialized junctions between neurons that are essential for the transmission of information. Synaptic dysfunction can occur due to mutations that alter the structure and function of synaptic components or abnormal expression levels of a synaptic protein. One class of synaptic proteins that are essential to their biology are cell adhesion proteins that connect the pre- and post-synaptic compartments. Neurexins are one type of synaptic cell adhesion molecule that have, recently, gained more pathological interest. Variants in both neurexins and their common binding partners, neuroligins, have been associated with several neuropsychiatric disorders. In this review, we summarize some of the key physiological functions of the neurexin protein family and the protein networks they are involved in. Furthermore, examination of published literature has implicated neurexins in both neuropsychiatric and neurodegenerative disorders. There is a clear link between neurexins and neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia. However, multiple expression studies have also shown changes in neurexin expression in several neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Therefore, this review highlights the potential importance of neurexins in brain disorders and the importance of doing more targeted studies on these genes and proteins.

J of Neuroscience Research

“…The neuroprotective effects of apelin/APJ axis have been significantly associated with improved behavioral effects in vivo . Apelin treatment was accompanied by a reduced motor impairment of 6‐OHDA‐induced rat models of PD (Haghparast et al., 2019). Compared to controls, apelin‐treated rats displayed improved motor skill learning and motor performance, better recovery in catalepsy time, as well as improved motor coordination and balance (Haghparast et al., 2019).…”

Section: The Effects Of Apelin/apj Axis On Motor and Cognitive Function In Pd In Vivomentioning

confidence: 99%

“…Apelin treatment was accompanied by a reduced motor impairment of 6‐OHDA‐induced rat models of PD (Haghparast et al., 2019). Compared to controls, apelin‐treated rats displayed improved motor skill learning and motor performance, better recovery in catalepsy time, as well as improved motor coordination and balance (Haghparast et al., 2019). These behavioral effects were associated with attenuation of dopaminergic neuronal death in the SN (Haghparast et al., 2019).…”

Section: The Effects Of Apelin/apj Axis On Motor and Cognitive Function In Pd In Vivomentioning

confidence: 99%

“…Compared to controls, apelin‐treated rats displayed improved motor skill learning and motor performance, better recovery in catalepsy time, as well as improved motor coordination and balance (Haghparast et al., 2019). These behavioral effects were associated with attenuation of dopaminergic neuronal death in the SN (Haghparast et al., 2019). In accordance, apomorphine‐induced rotational test has demonstrated that 6‐OHDA‐induced SN damage could be prevented by apelin‐13 in rat models of PD (Haghparast et al., 2018).…”

Section: The Effects Of Apelin/apj Axis On Motor and Cognitive Function In Pd In Vivomentioning

confidence: 99%

See 1 more Smart Citation

Impact of the apelin/APJ axis in the pathogenesis of Parkinson’s disease with therapeutic potential

Angelopoulou

Paudel

Bougea

et al. 2021

The pathogenesis of Parkinson's disease (PD) remains elusive. There is still no available disease‐modifying strategy against PD, whose management is mainly symptomatic. A growing amount of preclinical evidence shows that a complex interplay between autophagy dysregulation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, and excessive neuroinflammation underlies PD pathogenesis. Identifying key molecules linking these pathological cellular processes may substantially aid in our deeper understanding of PD pathophysiology and the development of novel effective therapeutic approaches. Emerging preclinical evidence indicates that apelin, an endogenous neuropeptide acting as a ligand of the orphan G protein‐coupled receptor APJ, may play a key neuroprotective role in PD pathogenesis, via inhibition of apoptosis and dopaminergic neuronal loss, autophagy enhancement, antioxidant effects, endoplasmic reticulum stress suppression, as well as prevention of synaptic dysregulation in the striatum, excessive neuroinflammation, and glutamate‐induced excitotoxicity. Underlying signaling pathways involve phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin, extracellular signal‐regulated kinase 1/2, and inositol requiring kinase 1α/XBP1/C/EBP homologous protein. Herein, we discuss the role of apelin/APJ axis and associated molecular mechanisms on the pathogenesis of PD in vitro and in vivo and provide evidence for its challenging therapeutic potential.