title: Current disease modifying approaches to treat Parkinson's disease.
abstract: Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candidates to counteract and possibly halt cell degeneration in PD. In particular, studies employing glial cell line-derived neurotrophic factor (GDNF) and its family member neurturin (NRTN), as well as the recently described cerebral dopamine neurotrophic factor (CDNF) and the mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown positive results in protecting and repairing dopaminergic neurons in various models of PD. Other substances with trophic actions in dopaminergic neurons include neuropeptides and small compounds that target different pathways impaired in PD, such as increased cell stress, protein handling defects, dysfunctional mitochondria and neuroinflammation. In this review, we will highlight the recent developments in this field with a focus on trophic factors and substances having the potential to beneficially influence the viability and functions of dopaminergic neurons as shown in preclinical or in animal models of PD.
authors.affiliation: Medicum, Department of Biochemistry and Developmental Biology, Medical Faculty, University of Helsinki, P.O.Box 63, 00014, Helsinki, Finland. dan.lindholm@helsinki.fi.|Minerva Medical Research Institute, Biomedicum-2 Helsinki, Tukholmankatu 8, 00290, Helsinki, Finland. dan.lindholm@helsinki.fi.
authors.forename: Dan
authors.initials: D
authors.lastname: Lindholm
authors.affiliation: Medicum, Department of Biochemistry and Developmental Biology, Medical Faculty, University of Helsinki, P.O.Box 63, 00014, Helsinki, Finland.|Minerva Medical Research Institute, Biomedicum-2 Helsinki, Tukholmankatu 8, 00290, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mäkelä
authors.affiliation: Division of Human Physiology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Liberto
authors.affiliation: Division of Human Physiology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudò
authors.affiliation: Division of Human Physiology, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Corso Tukory 129, 90134, Palermo, Italy.
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
authors.affiliation: Medicum, Department of Biochemistry and Developmental Biology, Medical Faculty, University of Helsinki, P.O.Box 63, 00014, Helsinki, Finland.
authors.forename: Ove
authors.initials: O
authors.lastname: Eriksson
authors.affiliation: Institute of Biotechnology, University of Helsinki, P.O.Box 56, Viikinkaari 9, 00014, Helsinki, Finland.
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051101:Neurturin / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000627:therapeutic use; D056811:Unfolded Protein Response; D051844:alpha-Synuclein / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C522217:CDNF protein, human; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D051101:Neurturin; D011994:Recombinant Proteins; D051844:alpha-Synuclein
keywords: Dopamine neurons; ER stress; Mitochondria; Neuroinflammation; Neuropeptides; Neurotrophic factors; Protein aggregation; α-Synuclein