Parkinson’s Disease: Insights from Drosophila Model

Abstract

Parkinson's disease (PD) is a medical condition that has been known since ancient times. It is the second most common neurodegenerative disorder affecting approximately 1% of the population over 50 years. It is characterized by both motor and non-motor symptoms. Most of PD cases are sporadic while 5-10% cases are familial. Environment factors such as exposure to pesticides, herbicides and other heavy metals are expected to be the main cause of sporadic form of the disease. Mutation of the susceptible genes such as SNCA, PINK1, PARKIN, DJ1, and others are considered to be the main cause of the familial form of disease. Drosophila offers many advantages for studying human neurodegenerative diseases and their underlying molecular and cellular pathology. Shorter life span; large number of progeny; conserved molecular mechanism(s) among fly, mice and human; availability of many techniques, and tools to manipulate gene expression makes drosophila a potential model system to understand the pathology associated with PD and to unravel underlying molecular mechanism(s) responsible for dopaminergic neurodegeneration in PD-understanding of which will be of potential assistance to develop therapeutic strategies to PD. In the present review, we made an effort to discuss the contribution of fly model to understand pathophysiology of PD, in understanding the biological functions of genes implicated in PD; to understand the gene-environment interaction in PD; and validation of clues that are generated through genome-wide association studies (GWAS) in human through fly; further to screen and develop potential therapeutic molecules for PD. In nutshell, fly has been a great model system which has immensely contributed to the biomedical research relating to understand and addressing the pathology of human neurological diseases in general and PD in particular.

Dietary Macronutrient Management to Treat Mitochondrial Dysfunction in Parkinson’s Disease

“…The ability to tightly control the reproduction, genetics, and physiology of an animal that shares 75% of its genes with humans has led to many discoveries into normal mitochondrial function as well as its role in disease [32]. Accordingly, Drosophila has been an excellent model for studying the role of mitochondria in PD pathology and treatment [33,34,35].…”

Sexual dysfunction precedes motor defects, dopaminergic neuronal degeneration, and impaired dopamine metabolism: Insights from Drosophila model of Parkinson’s disease

“…Immunostaining assay was performed following the protocol of Ayajuddin et al (2022). In brief, 5 days old male OK flies were fixed in 4% paraformaldehyde (PFA) containing 0.5% TritonX-100, at room temperature for 2 h. The brains were then washed 5 times for 15 min duration each (75 min) at room temperature with phosphate-buffered saline (PBS) containing 0.1% Triton-X 100 (PBST).…”

“…Then the brains were embedded in VECTASHIELD R mounting medium and proceeded for image acquisition on the same day. Mounting of the whole fly brain for fluorescence microscopy (Carl Zeiss, Axio Imager M2 with ZEN 2012 SP2 software, Germany) was done as described in Ayajuddin et al (2022).…”

“…Drosophila melanogaster has been used widely as a model organism to understand the pathophysiology of human disease (s) specifically neurodegenerative disorders (NDDs) like PD as several disease-causing genes and signaling pathways are conserved between fly and humans ( Reiter et al, 2001 ; Muñoz-Soriano and Paricio, 2011 ; Varga et al, 2014 ; Rahul and Siddique, 2022 ; Suzuki et al, 2022 ). The shorter life cycle (10–12 days at 25 ° C), a large number of progenies, established genetic methods, and molecular biology tools to manipulate genome and generate mutants and further perform loss and gain of function analysis make Drosophila an effective model system in biomedical research ( Ayajuddin et al, 2018 ). Drosophila models a network of behaviors that are closely connected to humans, such as courtship ( Dickson, 2008 ) which is believed to be one of the finest behaviors displayed by the fruit fly, and grooming ( Tauber et al, 2011 ).…”

Adult health and transition stage-specific rotenone-mediated Drosophila model of Parkinson’s disease: Impact on late-onset neurodegenerative disease models

“…Parkinson’s disease (PD) is a neurodegenerative disease (NDD) affecting the movement in the aging human population ( Tysnes and Storstein, 2017 ) and the second most common NDD affecting about 1% of the population over 50 years ( Ayajuddin et al, 2018 ), 1.5–2% over the age of 60 years, and 4% of the elderly individuals over the age of 80 years ( Marino et al, 2020 ). More than 6 million individuals across the globe are suffering from PD ( Armstrong and Okun, 2020 ).…”