Drosophila Models of Sporadic Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the most common cause of movement disorders and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. It is increasingly recognized as a complex group of disorders presenting widely heterogeneous symptoms and pathology. With the exception of the rare monogenic forms, the majority of PD cases result from an interaction between multiple genetic and environmental risk factors. The search for these risk factors and the development of preclinical animal models are in progress, aiming to provide mechanistic insights into the pathogenesis of PD. This review summarizes the studies that capitalize on modeling sporadic (i.e., nonfamilial) PD using Drosophila melanogaster and discusses their methodologies, new findings, and future perspectives.

UsingDrosophilaas a platform for drug discovery from natural products in Parkinson's disease

“…[105][106][107][108][109] These environmental toxin-induced models recapitulate the cardinal features of PD, including motor defects, dopaminergic neuron loss and the formation of Lewy bodies. 110 MPTP has been shown to selectively damage dopaminergic neurons due to mitochondrial dysfunction and oxidative stress. 111 The herbicide PQ-induced neurotoxicity is known to involve the generation of ROS, which leads to neuronal death.…”

Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor

“…Drosophila offers a powerful model system to investigate molecular mechanisms of PD pathogenesis in vivo, due to the abundance of genetic tools, the conservation of most PDrelated pathways and familial PD-linked genes, and its relatively simple nervous system 22,23 .…”

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“…The PD prevalence rate at present is 1-2 per 1000 of the population in the world 3 . Degeneration of dopamine neurons in the substantia nigra is the main causative factor behind PD 3 .…”

“…Neurodegeneration of dopamine neurons in PD occurs due to environmental factors, aging or due to genetic reasons 3 . Also genetic reasons may drive both familial as well as sporadic incidents of PD 3 .…”

“…Neurodegeneration of dopamine neurons in PD occurs due to environmental factors, aging or due to genetic reasons 3 . Also genetic reasons may drive both familial as well as sporadic incidents of PD 3 . Alpha-synuclein (-synuclein) gene mutation is one of the major genetic factors responsible for PD pathogenesis 4 .…”