Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5739165 | Progress in Neurobiology | 2017 | 76 Pages |
Abstract
Parkinson's disease is a progressive neurodegenerative disorder characterized by the degeneration of midbrain nigral dopaminergic neurons. Although its etiology remains unknown, the pathological role of several factors has been highlighted, namely oxidative stress, neuroinflammation, protein misfolding, and mitochondrial dysfunction, in addition to genetic predispositions. The current therapy is mainly symptomatic with l-DOPA aiming to replace dopamine. Novel therapeutic approaches are being investigated with the intention of influencing pathways leading to neuronal death and dysfunction. The present review summarizes three novel approaches, the use of which is promising in pre-clinical studies. Polyphenols have been shown to possess neuroprotective properties on account of their well-established antioxidative and anti-inflammatory actions but also due to their influence on protein misfolding and mitochondrial homeostasis. Within the amazing ancillary effects of antibiotics, their neuroprotective properties against neurodegenerative and neuroinflammatory processes are of great interest for the development of effective therapies against Parkinson's disease. Experimental evidence supports the potential of antibiotics as neuroprotective agents, being useful not only to prevent the formation of toxic α-synuclein oligomers but also to ameliorate mitochondrial dysfunction and neuroinflammation. Neuropeptides offer another approach with their diverse effects in the nervous system. Among them, pituitary adenylate cyclase-activating polypeptide, a member of the secretin/glucagon superfamily, has several advantageous effects in models of neurodegeneration, namely anti-apoptotic, anti-inflammatory and antioxidant actions, the combination of which offers a potent protective effect in dopaminergic neurons. Owing to their pleiotropic modes of action, these novel therapeutic candidates have potential in tackling the multidimensional features of Parkinson's disease.
Keywords
AMPKCREBNF-κB6-OHDALPSJnkDOXCATGFAPGSHGSTAβHO-1mTOR6-HydroxydopamineCOX-2ERKSNCVIPiNOSMCP-1IL-1βNGFLRRK2MPTPNMDAN-methyl-d-aspartatePINK1GPCRPACAPDCs1-methyl-4-phenylpyridiniumLC3GIRK2d-cycloserineIBA1Heme oxygenase-1NQO-1NTFsTLR4GRP78SOCS1LAMP2AMMP9DAergicNAD(P)H:quinone oxidoreductase-1γ-GCSHEK-293K-ATPhuman embryonic kidney-293lysosome-associated membrane protein 2aAMP-activated protein kinaseBDNFc-Jun N-terminal kinaseMPOG-protein-coupled receptorl-3,4-dihydroxyphenylalaninel-DOPAMAPKMPP+PTEN-induced putative kinase 1ROSβ-Amyloidγ-glutamylcysteine synthetaseAntioxidantsAntibioticsInterleukin-1 betaAlzheimer's diseaseParkinson's diseasesubstantia nigrasubstantia nigra pars compactatumor necrosis factor-alphaleucine-rich repeat kinase 2tyrosine hydroxylasedoxycyclineCNSDopamineDopaminergiclight chain 3SODBBBBlood–brain barriersuppressor of cytokine signaling 1inducible nitric oxide synthaseSuperoxide dismutasecentral nervous systemCyclooxygenase-2Neurotrophic factorsnerve growth factorBrain-derived neurotrophic factorTNF-αnuclear factor kappa-light-chain-enhancer of activated B cellslipopolysaccharideMatrix metalloproteinase 9ionized calcium binding adaptor molecule 1myeloperoxidaseNitric oxidemammalian target of rapamycinMitochondrial transmembrane potentialGlial fibrillary acidic proteinglucose-regulated protein 78monocyte chemoattractant protein-1mitogen-activated protein kinaseprostaglandinPolyphenolsvasoactive intestinal peptidepituitary adenylate cyclase-activating peptideCatalaseATP-sensitive K+ channelsextracellular signal-regulated kinaseGlutathioneglutathione S-transferaseReactive oxygen speciesToll-like receptor 4
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Authors
Dora Reglodi, Justine Renaud, Andrea Tamas, Yousef Tizabi, Sergio B. SocÃas, Elaine Del-Bel, Rita Raisman-Vozari,