The Role of Drosophila melanogaster (Fruit Fly) in Managing Neurodegenerative Disease in Functional Food and Neutraceuticals Research

Abstract

Fruit fly (Drosophila melanogaster) has emerged as a very useful model of neurodegenerative disease and could be more effective for therapeutic screening for neuroprotective properties of functional food and nutraceuticals. There have been no adequate screening models on functional food research in Africa. Limited studies have been reported on the use of D. melanogaster an alternative to the use of rodents and other animals in therapeutic screening of functional foods and nutraceuticals. The genomic similarities between D. melanogaster and humans, quick generation time, low maintenance requirements, and the accessibility of effective genetic tools, make the fruit fly a suitable research subject for complicated neurodegenerative ailments. However, there is more to be done in understanding complexity in human disease modeling, where the use of fly models will be the best alternative has not been explored. More outcry to conduct studies in disease-related models, the chronic diseases, such as cancer, GI disorders, and cardiovascular diseases, which are causes of death in most industrialized countries are required, although most of the diseases are linked with the intake of dietary fruits, vegetables, and whole grains. So the role of research models cannot be overemphasized, more studies are expected in finding better alternatives to the use of animals in the study of neurodegenerative diseases.

1. Introduction

In the prevention of chronic diseases such as neurodegenerative diseases, nutrition is critical; not just to meet nutritional requirements but more importantly to contribute to the total wellness of the consumer by either preventing and/or managing such disease conditions [1]. This has further promoted the concept of functional foods and nutraceuticals. The quality of nutritional studies largely depends on the research question addressed, the experimental design, the statistical power, and the composition of the experimental diets. However, while several studies abound on the huge abundance and diversity of functional foods, especially in tropical parts of the world, there is still a serious limitation to rapid and high experimental screening for neuroprotective properties of several functional foods, especially in developing nations. These limitations include modern, effective and accessible experimental models for rapid screening, cost of research, and ethical issues with animal use among others. The vast majority of nutritional studies in model organism have been conducted in laboratory rodents, such as mice and rats. Nutrient requirements for rodents are relatively well established including energy, lipids, fatty acids, carbohydrates, proteins, and amino acids as well as vitamins, minerals, and trace elements, but few cases are reported for the fruit flies [2, 3].

Fruit fly (D. melanogaster) has emerged as a very useful model of neurodegenerative disease and could be more effective for therapeutic screening for neuroprotective properties of functional food and nutraceuticals, especially from developing countries of tropical Africa [4]. D. melanogaster enables the possibility to conduct studies in disease-related models, not all experiments are required to be conducted with animal models, and therefore this review will focus on compiling scientific works done in the therapeutic screening for neuroprotective properties of functional food and nutraceuticals using D. melanogaster.

2. Functional foods and nutraceuticals

Food can be considered functional when it has a significant health effect that extends beyond basic traditional nutrition. Nutraceutical products are derived from foods containing the essential components, such as functional foods, which have therapeutic effects. Its beneficial components can be isolated and purified from plant, animal, or marine sources. Functional foods and nutraceuticals have attracted international interest and shaped a growing global market. They are often known as “functional foods;” nutraceuticals have led to intense controversy due to the fact that they blur the conventional dividing line between diet and medicine. Therefore, functional food provides the human body with the required quantity of basic needs and essential for healthy survival such as proteins, fats, carbohydrates, and vitamins [1]. It is considered “nutraceutical” when functional food helps in disease/disorder prevention and/or medication other than deficiency conditions such as anemia and other neurodegenerative diseases. Therefore, functional food may be used as a nutraceutical to another consumer [5].

When describing nutraceutical, they include products that come naturally with driven nutrients, dietary supplements, herbal products, and generally processed foods. While food nutraceuticals are generally dietary supplementary that are needed for human development. Dietary supplements give direction in which human develops; some epidemiological studies have emphasized on the relationship that exists between disease, lifestyle, and diet [6].

Hippocrates said, “Let your food be your medicine and your medicine be your food.” Nutraceuticals play an important role in biological processes such as cell proliferation, antioxidant defense, and gene expression. Nutraceuticals can delay the aging process and decrease the risk of situations such as cancer, heart disease, hypertension, excessive weight, high cholesterol, diabetes, osteoporosis, arthritis, insomnia, cataracts, constipation, indigestion, and many other lifestyle-related disorders [7].

Nutraceuticals are often said to be products that are extracted or purified from animal, plant, or marine sources, which have shown physiological benefits or are known to protect against chronic diseases.

Many studies have been published on therapeutic properties of functional foods, especially those of tropical African origins. In the last few decades, many interesting research publications have originated from Africa on therapeutic properties of several tropical functional foods. However, one major limitation to full evolution of functional food research in Africa has been adequate screening models [7].

Many studies have been carried out based on in vitro and vivo studies using of mouse and rats, but limited studies have been reported on the use of D. melanogaster, while we all know that not all vivo studies requires the use of rats, mouse, fish, and others.

Therefore, it is very important to explore more alternative studies tools. Fruit fly has emerged as the new alternative tool in the world for therapeutic screening of functional foods and nutraceuticals.

3. Classification of Functional foods and nutraceuticals

Depending on different parameters, many classifications of nutraceuticals were proposed. Depending on the established stage of nutraceuticals, nutraceuticals are classified as the following:

1. Nutraceuticals consist of compounds that offer therapeutic benefits in many types of research/epidemiology studies but are lacking compliance with large-scale clinical research.

2. Established nutraceuticals consist of compounds that exhibit health benefits well supported by clinical data [2].

They can be divided based on the nutraceutical source from which they are extracted or isolated:

1. Phytochemicals: extracted from plants or herbs, such as flavonoids.

2. Microbial extracted nutrients: such as vitamin A.

3. Nutrients of animal origin: extracted from livestock.

Nutraceuticals, generally, consist of polyunsaturated fatty acids, prebiotics, flavonoids, and vitamins.

Additional nutraceuticals are classifiable as the following:

• Nutritional enhancements: These formulas contain nutrients, for example, salt alone or with various preservatives.

• Functional foods: These are defined as food enhanced by promoters who promote optimum health and assist in decreasing the disease risk, such as oatmeal containing soluble fiber that reduces cholesterol levels. They are not just nutrients; in brief, they are foods enhanced with nutrients for health benefits [6].

Different researches have emerged that foods can be directly linked to neuro studies and balance of anxiety in the body, for example, potatoes, soybeans lentils, navy beans, yeasts, beans, chickpeas, kidney beans, catfish, milk, eggs, and beef are good sources of lysine. Studies have shown that lysine and amino acid inhibits the hyperactivation of serotonin receptors, which helps to induce anxiety-induced disorders that are caused by serotonin receptors in the intestinal tract due to their hyperstimulation [6].

Valine in its volume and shape roughly looks like threonine and it exhibits some stimulatory effects. Valine has important functions such as growth and repair of tissues, muscle metabolism, and nitrogen balance in the body. Valine is rich in some foods, such as mushrooms, sesame seeds, soy, peanuts, lentils, meat, fish, and cheese. Alanine removes toxins released during muscle breakdown so that the liver can metabolize them and remove them from the body. The cholesterol levels in the body are also checked by alanine [8].

In the human body, the main functions of aspargine are to support the nervous system to maintain equilibrium and regulate metabolism, and they also act as detoxifiers. Aspartic acid has its effect on cellular energy, so it is used to fight fatigue and depression. Sometimes aspartic acid plays a crucial role in manufacturing of other amino acids [9].

Cysteine has multiple functions, such as scavenging free radicals (as an antioxidant) and detoxifiers in the body. It is essential for healthy hair, nails, and skin.

The chronic diseases, such as cancer, GI disorders, and cardiovascular diseases, which are causes of death in most industrialized countries, and these high-risk conditions are reduced significantly with intake of dietary fruits, vegetables, and whole grains (Table 1).

	Phytochemicals in functional foods	Functional foods and neutraceuticals	Management of neurodegenerative diseases	References
1	Valine and alanine	Mushrooms, sesame seeds, soy, peanuts, lentils, meat, fish, and cheese.	Valine has important functions such as growth and repair of tissues, muscle metabolism, and nitrogen balance in the body.	[8]
			Alanine removes toxins released during muscle breakdown so that the liver can metabolize them and remove them from the body. The cholesterol levels in the body are also checked by alanine.	[8]
2	Cystine and glutamine		Boosting the immune system, good digestion, and proper brain function, suppression of hunger.	[10]
3	Proline	A meal with high carbohydrate levels.	For proper function of the brain and for formation of chemicals that enhance mental stability and mood serine is very essential.	[11]
4	Tyrosine and tryptophan	Sea vegetables, bananas, peanuts, cabbage mushrooms, watercress, parsley, and seeds.	Can promote good brain chemistry and influence the mood.	[12]
5	Selenocysteine	Rice, nuts, corn, oats, wheat, Brazil nuts, soybeans, chicken, cheese, fish, and seafood.
6	Vitamin C, Rutin, Ursolic acid, Lutein	Citrus fruits	which are very powerful and reduce the risk of heart stroke, coronary disease, oxidative stress, and inflammation. Citrus fruits help blood vessels to flow continuously so that sufficient oxygen is supplied to brain. Neuroprotection against cognitive deficits and brain damage.
7	Polyphenols	Apples	Some of the inflammatory damage to brain function can be reduced by flavonoids present in apples. Apples have antioxidants and quercetin, a photochemical that is good for the skin.
8	Resveratrol and Apolyphenol	Grape juice	which is present in grape juice, has many functions, such as the suppression of degenerative nerve disease, Alzheimer’s disease, viral infections, and cancer. Also help to coordinate cognitive functions.	[13]
9	Gallic acid	Straw berries	Beneficial effect on behavioral impairments after brain injury induced by ischemia/ reperfusion; cerebroprotective properties.

Table 1.

Phytochemicals in functional foods and nutraceuticals linked to control neurodegenerative diseases.

3.1 Nutraceutical future

Nutraceutical is frequently referred to in the 21st century as a more attractive functional food. By using nutraceutical tools, the physician of the future would have been a better source to offer preventive medical approaches. Nutraceuticals’ advances will encourage individualized nutrition personalized to the profile of a person to maximize health and comfort. The nutraceutical market shows that consumers are looking for minimal foods with additional dietary benefits and organoleptic value. In turn, this progress propels the expansion of global nutraceutical markets. In the new millennium, the evolving nutraceutical manufacturing appears destined to occupy the landscape. Its enormous growth and evolution have consequences for food, healthcare, industries of agriculture, and pharmaceutical [2].

4. D. melanogaster as a therapeutic screening model for functional food

4.1 Life cycle of D. melanogaster

From egg fertilization to adulthood, the drosophila life cycle spans roughly 10 – 12 days at 25°C. It is a holometabolous insect with significant physical variations between the larvae and adult (metamorphosis) (Figure 1). D. melanogaster is a model organism utilized mainly in developmental biology [14]. Four developmental stages are included throughout the Drosophila life cycle. Embryogenesis is a quick process that is finished 24 hours after the male sperm inseminates the oocyte. A one-cell embryo quickly develops into a syncytial embryo. Nuclear divisions and fast DNA replication take place in the early embryonic syncytium, producing up to 5000 nuclei per embryo. After nuclei migrate to the syncytial blastoderm’s periphery and undergo a process known as cleavage to produce the blastoderm, cellularization takes place. Three substages of the larval stage—totaling three instars—take place during the course of around 4 days (Figure 1). The majority of cell types are already functionally differentiated and growing as larvae. As a result, many biological queries can already be answered at the larval stage. For example, larvae have proved crucial for research on neural processes, such as memory formation. A simpler example is provided by the larval fly’s central nervous system, which has only 10,000 neurons compared to the adult fly’s more than 250,000 [15]. After the 3rd instar larva is encapsulated, the pupal stage begins and lasts for around fourth days. New structures are created after the lysis of many larval structures.

Figure 1.

Life cycle of Drosophila melanogaster.

The imaginal discs, which were created from undifferentiated larval cells, generate new structures. The adult head, legs, wings, thorax, and reproductive organs are derived from the imaginal discs. After the pupal case has closed, the adult fly comes out. The life expectancy is approximately 30 days, though it can vary depending on the climate. D. melanogaster is a good genetic model with relatively easy development in lab settings due to the huge number of eggs laid per female (100 eggs per day), which results in a large offspring after genetic crosses. Important advancements in the understanding of basic biological processes including aging, circadian rhythms, and behavioral research have resulted from the study of adult flies.

4.2 Reports on potentials of D. melanogaster as model organism

D. melanogaster, a fruit fly, is used as a model organism to research a variety of topics, from basic genetics through the development of tissues and organs. The human genome is 60% similar to the Drosophila genome, which is less redundant and shares 75% of the genes with flies that cause human disorders [16]. These characteristics, along with a quick generation time, low maintenance requirements, and the accessibility of effective genetic tools, make the fruit fly a suitable research subject for complicated processes important to biological and biomedical studies.

Model for insect control: For almost a century, scientists have utilized the common fruit fly, Drosophila melanogaster, as a model organism [17]. Thomas Hunt Morgan (1866–1945) and his students’ early research on the D. melanogaster resulted in important findings including sex-linked inheritance and the genetic mutations caused by ionizing radiation [18]. The first significant complex organism with its genome sequenced was D. melanogaster [19]. Most mammalian genes with D. melanogaster orthologs have been discovered to be crucial for typical mammalian development and function. The genomic similarities between D. melanogaster and humans have made D. melanogaster a more useful model for studying human biology and disease mechanisms. The majority of the genetic material is carried by three of the four chromosomes in the D. melanogaster genome, which contains more than 14,000 genes [20, 21]. According to estimates by Lloyd and Taylor [22], the fly possesses functional orthologs of close to 75% of disease-related genes in humans. At the nucleotide or protein sequence level, the overall similarity between fly and mammal homologs is typically around 40%; but, in conserved functional domains, it can be as high as 80–90% [23]. D. melanogaster has been used for purposes more than only genetic analysis.

It has been shown to be helpful for pharmacological research. Numerous drug-induced effects that were initially discovered in D. melanogaster have been confirmed in mammals [24, 25].

Drosophila melanogaster is a tractable model system for human disease and is used to analyze host interactions with recognized insect infections. Important information on the pathology of infection is provided by studies using insect pathogens6. In the food and nutrition industries, Drosophila melanogaster has been used as a model system to assess the possible health advantages of organic foods [26]. D. melanogaster-derived recombinant acetylcholinesterase (DmAChE) can be used to identify organophosphate and carbamate pesticides in food, vegetables, and the environment [27]. The creation of a three-electrode biosensor, as a new disposable screen-printed electrode, for quick detection of organophosphate and carbamate pesticides in vegetable and water samples, combines recombinant D. melanogaster AChE (R-DmAChE), multi-walled carbon nanotubes, and Prussian blue [28]. Alkylating compounds and other chemicals were tested on the D. melanogaster to see if they had any negative effects after numerous generations [17]. A Drosophila model was used to examine the toxicity and mutagenicity of the chemicals 1, 2,4,5-tetrachlorobenzene, 1,4,5-trichloro-2,6-nitrobenzene, pentachloronitrobenzene, methyl-l-(butyl-carbamoyl)-2-benzimidazole carbamate fungicides, and dimethyl-2,3,5,6-tetrachloroterephthalate [17]. Additionally, D. melanogaster has been used in resistance research on the insecticides cyclodiene and phenylpyrazole [29]. Endosulfan has negative effects on D. melanogaster both at the cellular and organismal levels. This research has shown that the use of D. melanogaster as animal model is a fantastic alternative for assessing the risk posed by environmental contaminants [30].

Alternative model organism in nutrigenomics: Currently, nutrigenomics encompasses not only nutrient-gene interactions but also nutrient-epigenetic, nutrient-proteomic, and nutrient-metabolomic interactions, as well as host-diet-microbiome interactions [31, 32]. This is how nutrigenomic research sits at the nexus of diet, health, and genomes [33, 34]. The model is the Drosophila melanogaster. Normal nucleotide and protein sequence homology between fly and mammalian species is around 40%; in some conserved functional areas, it can be as high as 90% [23, 35]. For the creation of mutant Drosophila melanogaster, chromosomal deletions and mutations targeting more than 80% of its genome have been created [36]. The advantages of Drosophila melanogaster, in addition to its well-characterized genome and the good availability of mutant and transgenic flies, include a quick life cycle (12 days for the succession of egg, maggot, pupa, and imago), a short lifespan (roughly 70–80 days), a small size (the ability to breed hundreds of individuals in small bottles), and a relatively simple generation of mutant animals in comparison to other organisms. Particularly, because of the presence of a fat body with adipocytes and conserved metabolic pathways involved in fat metabolism and insulin signaling; particularly, because of the presence of a fat body with adipocytes and conserved metabolic pathways involved in fat metabolism and insulin signaling.

Numerous studies using Drosophila melanogaster have examined problems connected to fat, such as cancer or cardiovascular failure [37, 38]. Genetic polymorphisms in the insulin/insulin-like growth factor signaling (IIS), and target of rapamycin (TOR) signaling pathway genes have been linked to changes in triglyceride levels and lipid storage brought on by consumption of high-fat and high-sugar diets [39, 40]. Due to its architecture and similar functions to those of mammals, the fruit fly also resembles a useful model for studying various tissues or organs. The Vienna Drosophila Research Center created an accessible RNAi knockdown fly line collection that targets around 90% of the fly genome, which is a significant accomplishment in D. melanogaster genetics research [23]. Caenorhabditis elegans has been used primarily for large-scale RNAi screens of gene function, despite the fact that this organism exhibits systemic RNAi, which makes it impossible to associate the gene interference with a particular cell type [41]. RNAi in Drosophila melanogaster can be activated by introducing a transgenic long double-stranded “hairpin” RNA because it is cell autonomous [41]. This tool can be used in conjunction with the GAL4/UAS system in Drosophila to inhibit the expression of a particular gene in a variety of cell types, making it possible to create conditional transgenic fly models [42]. This facilitates the study of the over- or under-expression of fly homolog genes and proteins, assisting in the development of fly models for the investigation of human diseases [43].

Model for toxicological studies: In the fields of genetics, biochemistry, cell biology, and developmental biology, D. melanogaster is frequently employed as a model organism. It has been employed as a model to clarify human diseases in recent decades, as well as incipiently for toxicological studies [44, 45, 46].

This fly has traditionally served as a genotoxicity model, but only recently has it been considered as a possible model for researching systemic toxicology or as a substitute model for toxicology research [44, 45]. The anatomical characteristics of D. melanogaster include wings and complex eyes. D. melanogaster is an important model to understand not only how the genes induce diseases, but also the discovery of the relation of such genes to diseases [20, 23, 47]. Of particular importance, more than 65–70% of human disease genes are present in D. melanogaster [23, 20]; Poddig [48, 49]. Due to its tiny body size and brief lifetime, D. melanogaster offers quick production times, convenience of usage, and straightforward laboratory maintenance in large quantities.

4.3 Role of D. melanogaster in biomedical research as model in functional food research

Drosophila for Cancer modeling: Since most signaling pathways controlling cell growth and invasion in mammals have a role with flies, it is possible to modify these pathways to create models that replicate the biology of tumors in an easy-to-use model organism such as Drosophila [50, 51]. Additionally, a quick assessment of the main role of conserved oncogenes, and tumor suppressor genes in an entire animal were made possible by the combination of genetic screens and the availability of potent recombination procedures [52].

Recent research employing Drosophila imaginal discs also looked at the processes involved in the recruitment of immune cells (macrophages) to the tumor mass, as well as the mechanisms governing the growth of epithelial tumors and their interaction with the surrounding stromal cells and TME [53, 54].

Epithelial tumors in Drosophila: The origin of over 90% of human malignancies is the epithelium [55]. The distinct cell architecture of epithelial tissues, which consists of junctions and apical and basolateral membrane domains is essential for the preservation of cell physiological functions, distinguishes them from other tissues. Early cancer symptoms do include a loss of cell adhesion and polarity, as well as an increase in cell mobility. Drosophila larval imaginal discs are the ideal model system to simulate the onset of epithelial cancer progression because they are a monolayer epithelium that is constrained apically by a squamous epithelium (peripodial membrane) and basally to the notum by a layer of myoblasts embedded in extracellular matrix. In fact, these larval organs resemble mammalian epithelia both morphologically and biochemically [56]. Additionally, the fruit fly preserves the main signaling pathways that control growth in humans, making it possible to use this animal model to analyze the characteristics of cancer [57]. The imaginal wing and eye discs have been successfully employed in recent years to explore tumor growth and invasion, the role of cancer genes, and chemical screens [58].

Model for COVID-19 research: Leading model organism D. melanogaster has been used to examine the biochemical and biological properties of human viruses and the effects they have on host cells [59, 60, 61]. The versatility of the model system and the viability of research using human viruses are some of the powerful features in Drosophila that shall be beneficial to explore biological events in a precise detail that may be difficult to overcome using higher animal models [16, 23, 59, 60, 61]. Therefore, it was anticipated that D. melanogaster would make an ideal model organism for study on COVID-19. As demonstrated in the cases of influenza A and dengue viruses [62, 63], this model organism may help us identify factors that affect host susceptibility to SARS-CoV-2 infection and determine whether those factors are clinically responsible for human susceptibility to SARS-CoV-2. As an alternative, one may investigate the mechanisms behind host innate immune activation in response to SARS-CoV-2 infection and see if changes to these processes might have an impact on how the infected hosts respond to the virus. D. melanogaster would undoubtedly be a helpful ally in COVID-19 research and the fight against COVID-19 if the correct questions were asked.

Model for anti-nephrolithiasis agents in kidney stone: Calcium oxalate nephrolithiasis, the 80% most common stone subtype, has a complicated origin [64, 65]. Predisposing variables include metabolic disorders such as hypercalcuria, hyperoxaluria, or hypocitraturia, as well as environmental elements such as diet. These etiological variables throw off the biochemical equilibrium of urine, which causes crystallization and the growth of stones [65]. Rat, mouse, porcine, and canine models, among others, have been created in the past for the research of nephrolithiasis [65]. Historically, the rat model of nephrolithiasis has been the most often used. In the rat model, lithogenic substances (ethylene glycol, ammonium chloride, or vitamin D3) are intraperitoneally injected to cause calculus development [66]. The application of this paradigm has led to inconsistent stone production and a variety of consequences. Additionally, the overall model utility is reduced due to the nephrotoxicity of the lithogenic agents [67, 68]. D. melanogaster is a particularly potent model due to its high reproductive rate, fully mapped, and largely understood genome, as well as the simplicity of its experimental design. Nephrocytes and Malpighian tubules (MTs), the two distinct parts of the DM renal system, exhibit a striking degree of structural and functional similarities to the human nephron. The fact that the stones created in the MT are also present in the feces may make it possible to detect stone creation in vivo without causing any harm [69].

5. Limitation of fruit fly in nutrition research

Even such fly models can have high degrees of conservation and validity, allowing for speedy screening and result interpretation, modeling complex human disease may be somewhat difficult because such fly models often express only particular components of the disease. It is also conceivable to see that some treatments that are harmful to flies may not be in people and vice versa due to variations in metabolism, despite what could seem to be a strong correlation between the toxicity of the two creatures [70].

The possibility that crucial pathogenetic elements are vertebrate-specific and might be overlooked in invertebrate models is a clear drawback of utilizing fly models. For instance, Drosophila melanogaster cannot provide a compelling model for immunological illnesses such as multiple sclerosis.

6. Composition of experimental diets given to D. melanogaster

A diet like cornmeal increases the lifespan of D. melanogaster, whereas diets high in free accessible carbs (saccharides) and cholesterol can shorten their lives. Uniform bottles and vials are preferred for simplicity of fly culture and transfer. There are numerous common D. melanogaster media compositions. For instance, in the lab, the flies are cared for and raised on a medium of cornmeal. (1%, w/v brewer’s yeast; 2%, w/v sucrose; 1%, w/v powdered milk; 1%, w/v agar; 0.08%, v/w nipagin) kept at a constant temperature and humidity (23 + 1°C and 60% relative humidity, respectively) for 12 hours of darkness and light. Li et al. [71] and Peng et al. [72] have used basal diets containing 105 g of cornmeal, 21 g of yeast, 105 g of glucose, and 13 g of agar; then, 0.4% of Ethyl 4-hydroxybenzoate was added to the diet in order to prevent mold growth [73].

Based on the dietary components specified in the study procedures, an investigation by a team of researchers showed the nutritional composition of more than 70 published diets used for D. melanogaster microbiome research [74]. It demonstrates that there are differences in diets and no fixed ration because the formulation for the recipe’s apparent norm is vague. Thus the dietary formulation for D. melanogaster may vary in composition in relation to the customary recipe for the study at hand.

7. Conclusion

D. melanogaster models can have high degrees of conservation and validity, allowing for speedy screening and result interpretation, modeling complex human disease may be somewhat difficult because such fly models often express only particular components of the disease. It is also conceivable to see that some treatments that are harmful to flies may not be in people and vice versa due to variations in metabolism, despite what could seem to be a strong correlation between the toxicity and physiology of the two creatures. The possibility that crucial pathogenetic elements related to neurodegenerative diseases and metabolic disorders are vertebrate-specific and might be overlooked in invertebrate models could be a setback in employing the use of fly models. There is need for more research on areas where the uses of fly models have not been explored like inability of provide a compelling model for immunological illnesses such as multiple sclerosis.