Drosophila melanogaster in Amyotrophic Lateral Sclerosis Research

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Krupa Hegde	--	2367	2022-10-27 14:43:58	\|
2	Reference format revised.	Lindsay Dong	Meta information modification	2367	2022-10-28 03:13:53	\|

Drosophila melanogaster in Amyotrophic Lateral Sclerosis Research

This entry is adapted from the peer-reviewed paper 10.3390/jdb10030036

Due to the availability of a vast array of genetic manipulation tools, its relatively short lifespan, and its ability to produce many progenies, D. melanogaster has provided the ability to conduct large-scale genetic screens to elucidate possible genetic and molecular interactions in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis (ALS). With regards to ALS, many of the gene mutations that have been discovered to be linked to the disease have been modeled in Drosophila to provide a look into a detailed model of pathogenesis.

ALS Drosophila genetics

1. Introduction

Thomas Morgan’s pioneering of the fruit fly as a model organism helped establish the baseline use of Drosophila melanogaster in biological research. Morgan and his team’s use of the fruit fly to define genetic principles catapulted this species to a famed model organism. This was compounded when Hermann Muller formulated the use of balancer chromosomes to maintain stocks with mutations on single chromosomes over many generations. Together, these developments cemented Drosophila as an ideal organism for genetic studies. Over time, various other genetic tools have been devised to study the role of genes in Drosophila further, including the Q-system ^[1], UAS-gal4 system ^[2] MiMIC ^[3], and CRISPR/Cas9 ^[4]. The prominence of using Drosophila for research was highlighted when Nusslein-Volhard, Wieschaus, and Lewis won the Nobel Prize for using Drosophila to study the roles of genes in embryonic development. The usefulness of Drosophila was further highlighted when the sequence of the Drosophila genome was released in March 2000. All of these together established Drosophila as a legitimate model for human health and disease studies, especially since the finding that approximately 77% of known human disease genes have orthologues in the fruit fly genome was unveiled ^[5]. Prominently, Drosophila has been used heavily in studying neurodegenerative diseases, including Huntington’s Disease, Parkinson’s disease, Alzheimer’s, and Amyotrophic Lateral Sclerosis (ALS).

2. Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is a currently incurable disease primarily characterized by the progressive degeneration of motor neurons. Physiological symptoms include localized muscle weakness, speech disturbances, fatigue, and possible fasciculations and cramps. Eventually, the progressive degeneration leads to respiratory failure—the main cause of death in ALS ^[6]. The prognosis for the disease is quite poor, with the median survival time from onset and detection to death ranging from 20 to 48 months. However, 10%–20% of ALS patients survive longer than 10 years after onset, which highlights the individuality of the disease ^[7]. ALS is subdivided into two main types: familial ALS (fALS) and sporadic ALS (sALS).

3. The Role of SOD1 in ALS

Superoxide dismutase 1 (SOD1) was the first protein reported to be associated with ALS ^[8] and current data shows that a variety of different mutations in SOD1 account for approximately 12–15% of fALS cases and 1% of sALS cases ^[9]. SOD1 normally exists as a homodimer that forms a heterodimer with a copper chaperone for SOD1 (CSS) for copper transfer.

By 1995, a fly model was developed utilizing mutants created by mutagenizing genetically marked chromosomes, SOD^F or SOD^S, with ethyl methanesulfonate, γ irradiation, or hybrid dysgenesis. This mutagenesis associated missense mutations located in SOD in Drosophila with lesser SOD enzymatic activity and suggested a dimer disequilibrium model in which SOD activity in mutants is lowered through the entrapment of wild-type (WT) subunits into heterodimers ^[10]. Additionally, researchers showed that the overexpression of SOD1 in the motor neuron extended the Drosophila lifespan and rescued the lifespan of a mutant that does not express any of the three Drosophila SODs ^[11].

Somewhat contrastingly, this association of SOD1 to Drosophila lifespan was shown to be related to ubiquitous overexpression of SOD1 and not to selective overexpression in the nervous system or muscle cells ^[12]. Surprisingly, neither pan-neuronal nor pan-glial overexpression of human SOD1 extended the lifespan of Drosophila; however, ubiquitous knockdown of SOD1 through RNAi resulted in reduced lifespan in flies. Furthermore, it was determined that the expression of WT or disease-linked mutants of human SOD1 (hSOD1) selectively in motor neurons brought about climbing defects, defective neural circuit electrophysiology, and accumulation of hSOD1 proteins in motor neurons ^[13]. These studies highlight the versatility of Drosophila models.

SOD1’s association with ALS in Drosophila was recently explored with a knock-in model, in which four human ALS-causing SOD1 mutations were engineered into the endogenous locus of Drosophila SOD1 (dSOD1). Doing this through homologous recombination is a testament to the versatility of Drosophila, especially when it comes to investigating the roles that genes play in various disease mechanisms. This knock-in model achieved ALS-like phenotypes without the overexpression of dSOD1. It resulted in flies exhibiting neurodegeneration, locomotor deficits, and the characteristic shortened lifespan similar to that seen in ALS. Furthermore, muscular atrophy and denervation were shown in two of these mutants, consistent with the characteristic symptoms in human ALS patients ^[14]. Further research using this Drosophila knock-in model has surmised the possibility that nonmotor neurons are also implicated in ALS. Both early and late-stage dSOD1 mutant flies were shown to have motor defects that can be mitigated by bone morphogenic protein signaling present within some interneurons ^[15].

Though Drosophila has served as a model organism for multiple studies showing various outcomes of the knockdown or overexpression of SOD1, a specific mechanism of disease has yet to be found. A Drosophila transgenic model expressing zinc-deficient hSOD1 was used to examine the cellular toxicity of the SOD1 mutation. The study found that the zinc-deficient mutants experienced a decrease in physical activity and deterioration of mitochondrial structure, which suggests a disease mechanism of zinc-deficient SOD1 mutations causing mitochondrial dysfunction ^[16]. Drosophila models have allowed for invaluable research into the SOD1 gene and its toxicity in relation to ALS.

4. Alsin’s Association with ALS

A second protein, Alsin, was found to be associated with ALS in 2001 ^[17]. It is encoded by the ALS2 gene. The protein is a guanine nucleotide exchange factor for the GTPase Rab5 ^[18]. A Drosophila model for Alsin-ALS was developed using the Drosophila ortholog, dALS2. Consistent with ALS in humans, the Drosophila mutants lacked approximately 30% of their coding sequence and showed a significant reduction in locomotion when compared to WT flies ^[19]. This locomotion reduction was rescued by ubiquitous WT dALS2 overexpression, which suggests a loss-of-function cause, shown through a Drosophila model ^[20].

5. The Role of VAP-B in ALS

In Drosophila, the VAPB homolog dVAP-33 controls boutons at the neuromuscular junction (NMJ) and causes postsynaptic glutamate receptor clustering. The UAS/Gal4 system was used in Drosophila to alter the expression of dVAP-33A in neurons and showed significant changes in the neuromuscular junction. Both hypomorphic and null mutations in dVAP-33A mutants showed a severe decrease in bouton numbers and an increase in bouton size while overexpression induced an increase in bouton number with a decrease in size. Mutants also displayed changes in glutamate receptors found at the NMJ with regard to subunit abundance and cluster size. This could suggest a mechanism of toxicity dependent on changes at the NMJ. These results found in Drosophila could prove to be highly corollary to humans due to the homologous nature between the human and the Drosophila VAPB protein, shown by the fact that the loss of dVAP-33A phenotypic changes are rescued by targeting the expression of hVAPB in Drosophila neurons ^[21].

More recently, a Drosophila model was established to investigate VAMP’s role in the ER and its association with ALS. dVAP-33A null mutant larvae were observed to have a substantial decrease in crawling speed when compared to genomic rescue controls, and it was found that a loss of dVAP-33A led to an accumulation of Atg8a-II in the brain, fat body, and salivary glands. Atg8a is associated with autophagy in Drosophila, and a transmission electron microscopy analysis of dVAP-33A mutant flies showed a dramatic accumulation of autophagosomes, lysosomes, and autolysosomes, thus proposing an association between autophagy and the mechanism of disease. More specifically, Drosophila data showed that a failure to connect the ER to the Golgi when VAPs are lost leads to an expansion of endosomes causing an accumulation of dysfunctional lysosomes and a failure of autophagic lysosomal degradation that leads to ER stress and possibly to ALS ^[22].

Another possible mechanism of disease with regards to VAPB was illustrated in Drosophila using loss of dVAP-33A mutants. These mutants were shown to have severe mitochondrial defects in adult muscles, suggesting a possible relation to mitochondrial dysfunction ^[23]. A mechanism of mitochondrial dysfunction would be consistent with previously mentioned studies regarding SOD1 research, illustrating common pathways between the two.

6. Drosophila’s Role in Developing an Understanding of TDP-43 and ALS

TAR DNA binding protein 43 (TDP-43) is an RNA/DNA binding protein that has been linked to RNA-related metabolism and processing. In 2006, TDP-43 was found to be a component of the insoluble inclusions in the brains of patients with ALS, and new research has found that a significant portion of ALS cases involve TDP-43 aggregation ^[24]. Many studies have utilized Drosophila, and its ortholog of TDP-43 TBPH, to help characterize this gene and its specific role in the pathogenesis of ALS, including characterizing whether or not the pathogenesis is caused by a gain or loss of function in the protein.

A potential model of TDP-43 toxicity was proposed using Drosophila. It was found that in adult flies, the accumulation of hTDP-43 in the cytoplasm is sufficient to cause degeneration, which is consistent with models of toxicity involving mislocalization seen in other ALS-related genes. It was also observed that the knockdown of TBPH (the drosophila homolog of TDP-43) caused no phenotypic change alone, suggesting a toxic gain of cytoplasmic TDP-43 could be a mechanism of pathogenesis. This is not certain, however, as a loss of nuclear TDP-43 function could also play a role in pathogenesis ^[25].

Drosophila has also been a model organism to investigate possible modifiers of hTDP-43. It was found that a group of genes involved in mitochondria and oxidative processes, such as uncoupling protein 4b (involved in the uncoupling components in the electron transport chain in reducing oxidative phosphorylation), were altered in flies expressing hTDP-43, an idea in line with the oxidative mechanisms of pathogenesis proposed in various SOD1 and VAMPB models ^[26].

7. The Role of FUS in the Pathogenesis of ALS

In 2009, a missense mutation in a new gene was found to be related to ALS cases by two separate groups independently ^[27]^[28]. This gene, FUS/TLS (fused in sarcoma, translated in liposarcoma—often referred to as FUS) is a predominantly nuclear protein that is implicated in DNA repair and transcription regulation, RNA splicing, and export to the cytoplasm ^[28]. It is an RNA-binding protein that has also been implicated in various cancers. Since then, multiple Drosophila models have been generated to further characterize the mutation and a possible mechanism of toxicity with relation to ALS.

A model of transgenic flies expressing ALS-mutant hFUS in various subpopulations of neurons showed age-dependent neurodegeneration, a characteristic of clinical and pathological features of FUS-ALS ^[29]. Moreover, flies generated through the UAS/gal4 system overexpressing mutant hFUS caused severe neurodegeneration in Drosophila eyes. A specific mutant, R521C, was associated with a decreased lifespan in flies ^[30]. Both of these studies have found that hFUS mutants express further degeneration than WT FUS ^[29]^[30].

Further studies examining the exact mechanism of disease have used Drosophila particularly in examining FUS’s relationship to the neuromuscular junction. In transgenic flies generated with the PhiC31 integration system that integrated hFUS or the Drosophila homolog in the Drosophila genome, it was found that FUS-related toxicity is dependent on the expression level of FUS in all examined tissues. It is proposed, due to morphological abnormalities found at the NMJ, that FUS causes toxicity by disrupting NMJs and possibly causing apoptosis in motor neurons ^[31].

8. C9orf72 and ALS—A Recent and Rapid Story

In 2011, a mutation was identified in ALS patients in the gene C9orf72 (Chromosome 9 open reading frame 72). The gene’s toxicity has been linked to a GGGGCC (G₄C₂) hexanucleotide repeat expansion within its first intron. This mutation has been linked to a wide array of ALS patients and is the most common genetic factor associated with sALS noted so far. Thus, examining the model of toxicity of this repeat expansion is essential in understanding the disease.

The first model of this mutation in Drosophila was developed in 2013. Transgenic flies were developed expressing EGFP (a reporter gene), 3 G₄C₂ ([G₄C₂]₃) repeats with EGFP, or 30 G₄C₂ ([G₄C₂]₃₀) repeats with EGFP. The expression of EGFP alone or [G₄C₂]₃-EGFP had no deleterious consequences, while the transient transfection expression of [G₄C₂]₃₀-EGFP caused lethality in early development. Moreover, when [G₄C₂]₃₀-EGFP expression was directed to the retina using GMR-gal4, severely disrupted eye morphology with various degrees of cell death, loss of pigmentation, and ommatidial disruption were noted. When expression of [G₄C₂]₃-EGFP and [G₄C₂]₃₀-EGFP was directed to the motor neurons, it was found that at day 28 post-eclosion, the [G₄C₂]₃₀-EGFP expressed a significant reduction in locomotion ^[32].

A second model was developed in 2013 to investigate the exact mechanism of toxicity of the repeat expansion. A primary question in this investigation was whether the toxicity caused by this mutation was a result of the repeat RNA produced by bidirectional translation of the hexanucleotide repeat expansion or the dipeptide repeat (DPR) proteins generated by repeat-associated translation of the repeat RNA. Drosophila with “RNA-only” repeats were generated by inserting stop codons in all sense and antisense frames. These were then compared to flies with pure protein repeats, and it was shown that flies with pure repeats expressed eye degeneration, whereas RNA-only flies did not express this degeneration ^[33]. This indicates that the toxicity is likely caused primarily by DPR proteins, which was then further investigated by constructing “protein-only” flies using alternative codons to those found in the G₄C₂ repeat. When comparing two arginine-containing DPR proteins to two neutral proteins, flies with the arginine-containing proteins expressed lethality and eye degeneration was not found in flies expressing the neutral proteins ^[33]. Thus, a model can be proposed where basic arginine-containing DPR proteins cause toxicity of the repeat expansion in Drosophila.

9. Drosophila’s Potential Pitfalls

Drosophila provides many advantages to studying neurodegeneration due to its simplicity and ease of manipulation. However, this simplicity is one of the major downsides of its use. Various Drosophila anatomy, including brain anatomy, differ drastically from humans, potentially influencing disease pathogenesis. It is also quite difficult to measure cognitive decline and differences in complex behavior with Drosophila ^[34] making studying neurodegenerative diseases specifically challenging. It is also worth recognizing that Drosophila, as an invertebrate, lacks complex features that may play a role in vertebrate neurodegeneration, including a less complex adaptive immune system that has been shown to be linked to ALS previously ^[35]^[36]. All of these aspects must be considered when researchers work in Drosophila; however, these pitfalls do not negate the versatility of Drosophila as a model system for studying ALS.

References

Riabinina, O.; Potter, C.J. The Q-system: A versatile expression system for Drosophila. Methods Mol. Biol. 2016, 1478, 53–78.
Duffy, J.B. GAL4 system in Drosophila: A fly geneticist’s Swiss army knife. Genesis 2002, 34, 1–15.
Venken, K.J.; Schulze, K.L.; Haelterman, N.A.; Pan, H.; He, Y.; Evans-Holm, M.; Carlson, J.W.; Levis, R.W.; Spradling, A.C.; Hoskins, R.A.; et al. MiMIC: A highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat. Methods 2011, 8, 737–743.
Gratz, S.J.; Rubinstein, C.D.; Harrison, M.M.; Wildonger, J.; O’Connor-Giles, K.M. CRISPR-Cas9 genome editing in Drosophila. Curr. Protoc. Mol. Biol. 2015, 111, 31.32.1–31.32.20.
Reiter, L.T.; Potocki, L.; Chien, S.; Gribskov, M.; Bier, E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001, 11, 1114–1125.
Zarei, S.; Carr, K.; Reiley, L.; Diaz, K.; Guerra, O.; Altamirano, P.F.; Pagani, W.; Lodin, D.; Orozco, G.; Chinea, A. A comprehensive review of amyotrophic lateral sclerosis. Surg. Neurol. Int. 2015, 6, 171.
Chiò, A.; Logroscino, G.; Hardiman, O.; Swingler, R.; Mitchell, D.; Beghi, E.; Traynor, B.G.; Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotroph. Lateral Scler. 2009, 10, 310–323.
Rosen, D.R. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993, 364, 362.
Renton, A.E.; Chiò, A.; Traynor, B.J. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 2014, 17, 17–23.
Phillips, J.P.; Tainer, J.A.; Getzoff, E.D.; Boulianne, G.L.; Kirby, K.; Hilliker, A.J. Subunit-destabilizing mutations in Drosophila copper/zinc superoxide dismutase: Neuropathology and a model of dimer dysequilibrium. Proc. Natl. Acad. Sci. USA 1995, 92, 8574–8578.
Parkes, T.L.; Elia, A.J.; Dickinson, D.; Hilliker, A.J.; Phillips, J.P.; Boulianne, G.L. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat. Genet. 1998, 19, 171–174.
Martin, I.; Jones, M.A.; Grotewiel, M. Manipulation of Sod1 expression ubiquitously, but not in the nervous system or muscle, impacts age-related parameters in Drosophila. FEBS Lett. 2009, 583, 2308–2314.
Watson, M.R.; Lagow, R.D.; Xu, K.; Zhang, B.; Bonini, N.M. A Drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1. J. Biol. Chem. 2008, 283, 24972–24981.
Şahin, A.; Held, A.; Bredvik, K.; Major, P.; Achilli, T.M.; Kerson, A.G.; Wharton, K.; Stilwell, G.; Reenan, R. Human SOD1 ALS mutations in a Drosophila knock-in model cause severe phenotypes and reveal dosage-sensitive gain- and loss-of-function components. Genetics 2017, 205, 707–723.
Held, A.; Major, P.; Sahin, A.; Reenan, R.A.; Lipscombe, D.; Wharton, K.A. Circuit dysfunction in SOD1-ALS model first detected in sensory feedback prior to motor neuron degeneration is alleviated by BMP signaling. J. Neurosci. 2019, 39, 2347–2364.
Bahadorani, S.; Mukai, S.T.; Rabie, J.; Beckman, J.S.; Phillips, J.P.; Hilliker, A.J. Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction. Neurobiol. Aging 2013, 34, 2322–2330.
Hadano, S.; Hand, C.K.; Osuga, H.; Yanagisawa, Y.; Otomo, A.; Devon, R.S.; Miyamoto, N.; Showguchi-Miyata, J.; Okada, Y.; Figlewicz, D.A.; et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet. 2001, 29, 166–173.
Otomo, A.; Hadano, S.; Okada, T.; Mizumura, H.; Kunita, R.; Nishijima, H.; Showguchi-Miyata, J.; Yanagisawa, Y.; Kohiki, E.; Suga, E.; et al. ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum. Mol. Genet. 2003, 12, 1671–1687.
Takayama, Y.; Itoh, R.E.; Tsuyama, T.; Uemura, T. Age-dependent deterioration of locomotion in Drosophila melanogaster deficient in the homologue of amyotrophic lateral sclerosis 2. Genes Cells 2014, 19, 464–477.
Casci, I.; Pandey, U.B. A fruitful endeavor: Modeling ALS in the fruit fly. Brain Res. 2015, 1607, 47–74.
Chai, A.; Withers, J.; Koh, Y.H.; Parry, K.; Bao, H.; Zhang, B.; Budnik, V.; Pennetta, G. hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction. Hum. Mol. Genet. 2008, 17, 266–280.
Mao, D.; Lin, G.; Tepe, B.; Zuo, Z.; Tan, K.L.; Senturk, M.; Zhang, S.; Arenkiel, B.R.; Sardiello, M.; Bellen, H.J. VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway. Autophagy 2019, 15, 1214–1233.
Han, S.M.; Tsuda, H.; Yang, Y.; Vibbert, J.; Cottee, P.; Lee, S.J.; Winek, J.; Haueter, C.; Bellen, H.J.; Miller, M.A. Secreted VAPB/ALS8 major sperm protein domains modulate mitochondrial localization and morphology via growth cone guidance receptors. Dev. Cell 2012, 22, 348–362.
Prasad, A.; Bharathi, V.; Sivalingam, V.; Girdhar, A.; Patel, B.K. Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis. Front. Mol. Neurosci. 2019, 12, 25.
Ritson, G.P.; Custer, S.K.; Freibaum, B.D.; Guinto, J.B.; Geffel, D.; Moore, J.; Tang, W.; Winton, M.J.; Neumann, M.; Trojanowski, J.Q.; et al. TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97. J. Neurosci. 2010, 30, 7729–7739.
Zhan, L.; Hanson, K.A.; Kim, S.H.; Tare, A.; Tibbetts, R.S. Identification of genetic modifiers of TDP-43 neurotoxicity in Drosophila. PLoS ONE 2013, 8, e57214.
Kwiatkowski, T.J.; Bosco, D.A.; Leclerc, A.L.; Tamrazian, E.; Vanderburg, C.R.; Russ, C.; Davis, A.; Gilchrist, J.; Kasarskis, E.J.; Munsat, T.; et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323, 1205–1208.
Vance, C.; Rogelj, B.; Hortobágyi, T.; De Vos, K.J.; Nishimura, A.L.; Sreedharan, J.; Hu, X.; Smith, B.; Ruddy, D.; Wright, P.; et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323, 1208–1211.
Chen, Y.; Yang, M.; Deng, J.; Chen, X.; Ye, Y.; Zhu, L.; Liu, J.; Ye, H.; Shen, Y.; Li, Y.; et al. Expression of human FUS protein in Drosophila leads to progressive neurodegeneration. Protein Cell 2011, 2, 477–486.
Lanson, N.A.; Maltare, A.; King, H.; Smith, R.; Kim, J.H.; Taylor, J.P.; Lloyd, T.E.; Pandey, U.B. A Drosophila model of FUS-related neurodegeneration reveals genetic interaction between FUS and TDP-43. Hum. Mol. Genet. 2011, 20, 2510–2523.
Xia, R.; Liu, Y.; Yang, L.; Gal, J.; Zhu, H.; Jia, J. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS. Mol. Neurodegener. 2012, 7, 10.
Xu, Z.; Poidevin, M.; Li, X.; Li, Y.; Shu, L.; Nelson, D.L.; Li, H.; Hales, C.M.; Gearing, M.; Wingo, T.S.; et al. Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc. Natl. Acad. Sci. USA 2013, 110, 7778–7783.
Mizielinska, S.; Grönke, S.; Niccoli, T.; Ridler, C.E.; Clayton, E.L.; Devoy, A.; Moens, T.; Norona, F.E.; Woollacott, I.O.; Pietrzyk, J.; et al. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 2014, 345, 1192–1194.
Prüßing, K.; Voigt, A.; Schulz, J.B. Drosophila melanogaster as a model organism for Alzheimer’s disease. Mol. Neurodegener. 2013, 8, 35.
Jeibmann, A.; Paulus, W. Drosophila melanogaster as a model organism of brain diseases. Int. J. Mol. Sci. 2009, 10, 407–440.
McCombe, P.A.; Lee, J.D.; Woodruff, T.M.; Henderson, R.D. The peripheral immune system and amyotrophic lateral sclerosis. Front. Neurol. 2020, 11, 279.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Developmental Biology

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Krupa N. Hegde

Ajay Srivastava

View Times: 407

Update Date: 28 Oct 2022

Table of Contents

Video Upload Options

Confirm