%0 Journal Article
%T Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies
%A Ver¨®nica Mu£¿oz-Soriano
%A Nuria Paricio
%J Parkinson's Disease
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/520640
%X Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. 1. Introduction Parkinson¡¯s disease (PD) is the second most common neurodegenerative disorder affecting more than 1% of the population over age 60. Clinically, it is characterized by locomotor defects such as muscle rigidity, bradykinesia, postural instability, and tremor. The principal neuropathology that gives rise to these motor defects is the progressive and selective loss of dopaminergic (DA) neurons in the Substantia nigra pars compacta, which causes a deficiency of brain dopamine content. Another pathological hallmark of this disorder is the presence of cytoplasmic inclusions in the surviving DA neurons called Lewy bodies (LBs), which are mainly composed of ¦Á-Synuclein and ubiquitin among other proteins [1, 2]. However, it has been shown that such structures are not present in some genetic forms of PD. Although the majority of PD cases are sporadic and are probably caused by a combination of risk factors like the aging process, genetic propensity, and environmental exposures, few environmental triggers have so far been identified. Weak associations between PD and exposure to environmental toxins or herbicides and pesticides have been reported [2], and several toxin-induced PD models have been developed [3]. However, epidemiological studies have also demonstrated the contribution of genetic factors in the pathogenesis of PD. Indeed, during the last decade, several loci whose mutations are causative of rare familial forms of the disease have been identified, which account for 5%¨C10% of all PD cases. These genes include
%U http://www.hindawi.com/journals/pd/2011/520640/