Table 1.

Brief characteristics, advantages, and disadvantages of the model objects.

	Yeast	Fruit fly	Nematode	Zebrafish	Minipigs	Dogs	Nonhuman primates
General characteristics of the model object
Taxonomy	Unicellular fungi	Invertebrates, insects	Invertebrates, roundworms	Vertebrates, fish	Vertebrates, mammals	Vertebrates, mammals	Vertebrates, mammals
Life span	From several days to 2 weeks	About 2 month	15–25 days	Max. 2 years.	10–15 years	10–13 years	5–40 years for different species
The presence and complexity of the nervous system	Absent	The presence of various types of glial and neuronal cells (including dopaminergic), a blood–brain barrier, motor neurons, and interneurons	The presence of 302 nerve cells, which have been characterized in detail regarding their function and synaptic contacts using dopamine, serotonin, glutamate, acetylcholine, and GABA as neurotransmitters	The brain consists of three sections (forebrain, midbrain, and hindbrain) and is separated from the remainder of the body by the blood–brain barrier. Dopaminergic neurons were found in the posterior tuberculum, which can be considered as an analog of the substantia nigra in mammals.	The high similarity of the brain structure between humans and minipigs, as well as the large size of the substantia nigra and striatum in minipigs	The high similarity of the brain structure between humans and dogs, as well as the large size of the substantia nigra and striatum	The high similarity of the brain structure between humans and primates, as well as the large size of the substantia nigra and striatum
Possibility to study motor behavior	Absent	Climbing activity, pattern of movement, spontaneous locomotor activity	The analysis of worm mobility after starvation: “basal slowing response” and “enhanced slowing response”, Chemotaxis, area-restricted search behavior, swim-to-crawl transition, Dauer-dependent behavior, mechanosensory responses, fecundity, and rate of defecation.	Deficits in evoked swimming response (bradykinesia) Decrease in total distance moved and swimming velocity (bradykinesia) Increase in number and duration of freezing episodes (dyskinesia).	Analysis of motor behavior: walking test, Hurdle test, open field locomotor activity	Locomotor activity in open field, walking test.	Parkinson’s disease rating scale (PRDS) for primates.
Simplicity and cost	+ (The most simple and inexpensive)	+ +	+ +	+ + + +	+ + + + + +	+ + + + + +	+ + + + + + + + + + (The most difficult and expensive)
Genetic models
Genome sequencing and annotation	YES	YES	YES	YES	YES	YES	YES
Similarity to the human genome	LOW	LOW	LOW	LIMITED	HIGH	HIGH	HIGH
Existence of genetic models	Exists	Exists	Exists	Exists	Exists, but not widespread	A natural mutation in ATP13A2 gene	NO
The main genes studied, homologous to human	SNCA, LRRK2, PRKN, PINK1, PARK7, VPS35, EIF4G1, ATP13A2	SNCA, LRRK2, PRKN, PINK1, PARK7, VPS35, GBA	SNCA, LRRK2, PINK1, PRKN, PARK7, ATP13A2	SNCA, LRRK2, PRKN, PINK1, ATP13A2	SNCA, PINK1/ PARK7/PRKN	ATP13A2	NO
Methods	knockout, knockdown, and overexpression, transgenic (mutant) animals	knockout, knockdown, and overexpression, transgenic (mutant) animals	knockout, knockdown, and overexpression, transgenic (mutant) animals	knockout, knockdown, and overexpression, transgenic (mutant) animals; the technology based on morpholino antisense oligonucleotides.	knockout, transgenic (mutant) animals	A natural mutation	NO
Collection of mutant lines of animals	Yeast Insertional Mutant Collection	The presence of a large collection of fruit fly lines with various mutations.	The presence of a large collection of mutant nematode lines	The presence of collections of D. rerio lines with various mutations	Absent	Absent	Absent
Application area	Analysis of selected genes / proteins associated with the development of the disease. Primary screening for new drugs.	Analysis of selected genes / proteins associated with the development of the disease	Analysis of molecular mechanisms of neurodegeneration associated with genes of monogenic forms of Parkinson’s disease	Analysis of molecular mechanisms of neurodegeneration associated with genes of monogenic forms of Parkinson’s disease; search for genes associated with neuroprotection	Comprehensive molecular biological and biochemical analysis; positron emission tomography analysis of brain structures, to monitor the development of neurodegeneration and changes in the nervous system, to correct neurodegenerative changes	Comprehensive molecular biological and biochemical analysis; a study of possible microbiome involvement in neurodegeneration	NO
Toxicity models
Existence	NO	Exists, but not widespread	Exists	Exists	Exists	NO	Exists
Toxins	NO	The rotenone and MPTP	6-hydroxydopamine, MPTP, paraquat, and rotenone	6-hydroxydopamine, MPTP, paraquat, and rotenone	6-hydroxydopamine, MPTP	NO	MPTPSNCA
Methods	NO	Addition of a toxin into the food	Addition of a toxin into the food	Intraperitoneal administration or addition of a toxin into the water	Unilateral injection of the toxin into the nigrostriatal pathway, a micropump-based chronic continuous MPTP administration	NO	Acute and chronic MPTP administration. SNCA as pure fibrillar protein or AV-based expression cassette
Application area	NO	Toxic models in the future can be used to search for new antiparkinsonian drugs	Search for new toxins that damage dopaminergic neurons; Analysis of biologically active substances; Study of microbiome	Screening for compounds with neuroprotective activity; Assessment of the potential neurotoxicity of normal metabolites, new pesticides, and other newly synthesized chemical compounds	Positron emission tomography analysis of brain structures for monitoring of the development of neurodegeneration, changes in the nervous system, and correction of neurodegenerative changes; the analysis of new therapeutic approaches for PD	NO	Development of new treatments for Parkinson’s disease associated with the use of deep brain stimulation, transplantation of neuronal cells into the substantia nigra and striatum, and for testing newly developed drugs in the last stages of preclinical studies
Advantages and disadvantages
Advantages	Simple system. The ability to obtain various mutations in genes associated with the development of the disease. Possibility of studying protein-protein interactions, searching for new candidate disease genes. Rapid initial screening of new potential neuroprotective drugs	A relatively simple and well-established system. The presence of large collections of mutant lines. Possibility of using both genetic and toxic models. The presence of a well-studied nervous system. There are dopaminergic neurons. Short lifespan. Possibility to study the relationship between aging and neurodegeneration	Ability to use a wide range of genetic and toxic models. Well-characterized nervous system, presence of neurons of different energies. Possibility of analyzing motor behavior. Short lifespan and the ability to analyze neurodegenerative changes in animals of different ages. Ease of maintenance and reproduction, low cost.	Ability to use a wide range of genetic and toxic models. Sufficiently high homology with the human genome, there are orthologs for most of the genes associated with the development of PD. A detailed description of the nervous system, the presence of neurons of different energies. Possibility to analyze motor behavior.	The high similarity of metabolism in general and organization of the nervous system to human analogs. Possibility of visualization of substantia nigra during PET scanning. Possibility of using toxic and genetic models. Possibility of testing antiparkinsonian drugs and other therapies.	Natural mutations in the genes of familial forms of PD, which make it possible to study manifestations in ontogenesis.	Possibility to analyze the clinical phenotype as close as possible to the clinical phenotype of PD in humans. Development of protocols for new methods of therapy on animals as close to humans as possible.
Disadvantages	Unicellular organism. The nervous system is completely absent. There are no orthologs for a number of genes that are fundamentally important for PD, primarily, orthologs of the synuclein gene.	Lack of orthologs for a number of genes that are fundamentally important for PD, primarily orthologs of synuclein genes. A fundamentally different organization of the nervous system in comparison with vertebrates and humans.	Lack of orthologs for a number of genes important for the development of PD. The ortholog of the synuclein genes is absent. There are significant differences in the organization of the nervous system from higher vertebrates.	More difficult conditions for keeping in comparison with nematodes and fruit flies. Longer lifespan, which complicates the study of the effects of aging on neurodegeneration processes.	Very limited range of genetic models. Relative complexity and high cost of keeping the animals. Limited opportunities to study the role of aging in the development of PD.	A very limited range of natural mutations. Lack of genetic models with targeted modification of candidate disease genes and toxic models. Limited opportunities to study the role of aging in the development of Parkinson’s disease.	Toxic models only. Long duration of the experiment. Very high cost of modeling. Problems with using large samples. Limited opportunities to study the role of aging in the development of Parkinson’s disease.