Monoamine oxidase and α-synuclein as targets in Parkinson's disease therapy.
The degeneration of dopaminergic neurons in Parkinson's disease (PD) is suggested to be associated with the generation of cytotoxic products from dopamine (DA) metabolism and the formation of fibrillar inclusions of the protein α-synuclein (AS). Despite of the role of AS in the pathogenesis of PD is not completely understood, the stabilization of nontoxic aggregates could represent a potential therapeutic route. In respect to the DA metabolism, a well-established strategy is the inhibition of the enzyme monoamine oxidase, which is responsible to catalyze the major route of inactivation of neurotransmitters. Although pharmacological strategies to treat different aspects of the parkinsonian condition are under investigation, the development of multifunctional molecules that act simultaneously on different targets associated to PD has gained attention only recently. In this work we examine the biochemical properties of synthetic and natural molecules that are capable of interfering on both DA system (via monoamine oxidase inhibition) and AS fibrillation.
Department of Physical Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Av. Athos Silveira Ramos 149, CT, A407 Cidade Universitária, Rio de Janeiro 21941-909, Brazil.
Cristian
C
Follmer
D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
D008996:Monoamine Oxidase Inhibitors; D051844:alpha-Synuclein; D008995:Monoamine Oxidase
Parkinson’s disease; dopamine; fibrils; monoamine oxidase; oxidative stress; protofibrils; α-synuclein