title: Brain aging and Parkinson's disease: New therapeutic approaches using drug delivery systems.
abstract: The etiology and pathogenesis of Parkinson's disease (PD) is unknown, aging being the strongest risk factor for brain degeneration. Understanding PD pathogenesis and how aging increases the risk of disease would aid the development of therapies able to slow or prevent the progression of this neurodegenerative disorder. In this review we provide an overview of the most promising therapeutic targets and strategies to delay the loss of dopaminergic neurons observed both in PD and aging. Among them, handling alpha-synuclein toxicity, enhancing proteasome and lysosome clearance, ameliorating mitochondrial disruptions and modifying the glial environment are so far the most promising candidates. These new and conventional drugs may present problems related to their labile nature and to the difficulties in reaching the brain. Thus, we highlight the latest types of drug delivery system (DDS)-based strategies for PD treatment, including DDS for local and systemic drug delivery. Finally, the ongoing challenges for the discovery of new targets and the opportunities for DDS-based therapies to improve and efficacious PD therapy will be discussed.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Navarra, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez-Nogales
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Navarra, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Garbayo
authors.affiliation: Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: Carmona-Abellán
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain; Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research (CIMA), University of Navarra, Spain.
authors.forename: M R
authors.initials: MR
authors.lastname: Luquin
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Navarra, Spain; Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain. Electronic address: mjblanco@unav.es.
authors.forename: M J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000375:Aging / Q000502:physiology*; D000975:Antioxidants / Q000008:administration & dosage; D001921:Brain / Q000503:physiopathology*; D004298:Dopamine / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D009414:Nerve Growth Factors / Q000008:administration & dosage; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D010455:Peptides / Q000008:administration & dosage; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D018491:Dopamine Agonists; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D010455:Peptides; D051844:alpha-Synuclein; D046988:Proteasome Endopeptidase Complex; D004298:Dopamine
keywords: Aging; Alpha-synuclein; Drug delivery systems; GDNF; Micro/nanoparticles; Parkinson disease; Therapeutic targets