title: Novel tactics for neuroprotection in Parkinson's disease: Role of antibiotics, polyphenols and neuropeptides.
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.
authors.affiliation: Department of Anatomy, MTA-PTE PACAP Lendulet Research Team, University of Pecs, Pecs, Hungary. Electronic address: dora.reglodi@aok.pte.hu.
authors.forename: Dora
authors.initials: D
authors.lastname: Reglodi
authors.affiliation: Department of Medical Biology, Université du Québec, Trois-Rivières, QC, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Renaud
authors.affiliation: Department of Anatomy, MTA-PTE PACAP Lendulet Research Team, University of Pecs, Pecs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamas
authors.affiliation: Department of Pharmacology, Howard University College of Medicine, Washington, DC, United States.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Tizabi
authors.affiliation: Sorbonne Université UPMC UM75 INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris, France; Instituto Superior de Investigaciones Biológicas (INSIBIO), Universidad Nacional de Tucumán-CONICET, Tucumán, Argentina.
authors.forename: Sergio B
authors.initials: SB
authors.lastname: Socías
authors.affiliation: University of São Paulo School of Odontology of Ribeirao Preto, Department of Morphology, Physiology and Pathology, Av. Café S/N, 14040-904 Ribeirão Preto, SP, Brazil; University of São Paulo, Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Del-Bel
authors.affiliation: Sorbonne Université UPMC UM75 INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Raisman-Vozari
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D006801:Humans; D009479:Neuropeptides / Q000494:pharmacology*; D000066829:Neuroprotection / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease; D059808:Polyphenols / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D009479:Neuropeptides; D018696:Neuroprotective Agents; D059808:Polyphenols
keywords: Antibiotics; Antioxidants; PACAP; Polyphenols