Chapters authored
Understanding Pathophysiology of Sporadic Parkinson's Disease in Drosophila Model: Potential Opportunities and Notable Limitations By Priyanka Modi, Ayajuddin Mohamad, Limamanen Phom, Zevelou
Koza, Abhik Das, Rahul Chaurasia, Saikat Samadder, Bovito Achumi, Muralidhara, Rajesh Singh Pukhrambam and Sarat Chandra
Yenisetti
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over age 50. PD is widely accepted as a multifactorial disease with both genetic and environmental contributions. Despite extensive research conducted in the area the precise etiological factors responsible remain elusive. In about 95% Parkinsonism is considered to have a sporadic component. There are currently no established curative, preventative, or disease-modifying interventions, stemming from a poor understanding of the molecular mechanisms of pathogenesis. Here lies the importance of animal models. Pharmacological insults cause Parkinsonian like phenotypes in Drosophila, thereby modelling sporadic PD. The pesticides paraquat and rotenone induced oxidative damage causing cluster specific DA neuron loss together with motor deficits. Studies in fly PD model have deciphered that signaling pathways such as phosphatidylinositol 3-kinase (PI3K/Akt and target of rapamycin (TOR), c-Jun N-terminal kinase (JNK) have been defective. Further, these studies have demonstrated that fruit fly can be a potential model to screen chemical compounds for their neuroprotective efficacy.
Part of the book: Challenges in Parkinson's Disease
Parkinson’s Disease: Insights from Drosophila Model By Mohamad Ayajuddin, Abhik Das, Limamanen Phom, Priyanka Modi,
Rahul Chaurasia, Zevelou Koza, Abuno Thepa, Nukshimenla Jamir,
Pukhrambam Rajesh Singh, Sentinungla Longkumer, Pardeshi Lal
and Sarat Chandra Yenisetti
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.
Part of the book: Drosophila melanogaster
Sexual Dysfunction in Neurological Disorders with Special Emphasis on Parkinson’s Disease: Insights from Clinical Studies and Animal Models By Zevelou Koza, Padmanabhan S. Rajani, Muralidhara, Ajaikumar B. Kunnumakkara and Sarat Chandra Yenisetti
Epidemiological studies illustrate that sexual dysfunction (SD) is common among the majority of patients suffering from neurological disorders (NLDs). However, our understanding of the SD in NLDs is in its infancy. Our effort in this review article reveals how the clinical studies illustrate different phenotypes relating to SD in both men and women suffering from NLDs, with special reference to PD, and how the development of animal models will provide a fantastic opportunity to decipher mechanistic insights into the biological and molecular processes of SD, understanding of which is critical to figure out the causes of SD and to develop therapeutic strategies either by targeting molecular players or altering and/or regulating the profiles of involved genetic targets. Specific emphasis is placed on dopamine-dependent and independent mechanism(s) of SD among PD patients, which is important because certain critical dopamine-independent phenotypes are yet to be characterized and understood in order to decipher the comprehensive pathophysiology of PD. Synergic efforts of both clinicians and bench scientists in this critical direction would significantly improve the quality of life of sufferers of NLDs who are already burdened. This knowledge relating to SD will help us to make one more step in reducing the burden of disease.
Part of the book: Parkinson’s Disease