Development of PD Modeling Viruses

Parkinson's disease (PD) is a degenerative disease that increases in incidence with age. The main pathological change in PD is the degenerative death of dopamine (DA) neurons in the substantia nigra of the midbrain, which leads to a significant reduction in striatal DA content. Alfa Cytology provides a stable platform for the study of PD pathology by creating PD models with viral vectors overexpressing α-synuclein in the substantia nigra.

We provide PD modeling services and modeling-related viral products

α-Synuclein is a soluble protein expressed in the presynaptic and perinuclear areas of the central nervous system, closely related to PD's pathogenesis and dysfunction. It is a major component of Lewy bodies. We can establish a PD rat model by applying a brain stereotactic technique to inject rAAV9X-type viruses carrying wild-type and mutant sequences of α-synuclein into the substantia nigra region of the midbrain of rats and achieve gene overexpression at the corresponding sites. We can evaluate the model from ethology tissue pathology and biochemistry perspectives.

Moulding methods	Animals
Peripheral or intracerebral injection of MPTP	Rat / Mouse
6-OHDA injection in striatum-nigrostriatal system	Rat / Mouse
Overexpression of α-synuclein in the substantia nigra by viral vectors	Rat

PD modelling-related products

Name	Serotype
PFD-rAAV-SYN (BrainVTA) -EGFP	AAV2 / 9
PFD-rAAV-SYN (BrainVTA) -SNCA (WT)	AAV2 / 9
PFD-rAAV-SYN (BrainVTA) -SNCA (A30P)	AAV2 / 9
PFD-rAAV-SYN (BrainVTA) -SNCA (A53T)	AAV2 / 9

Technical advantages

Targeting specific brain regions.
Transgenic expression can be performed in adult animals, avoiding the influence of compensatory mechanisms during development.
Disease models can be prepared at different doses, in different species (rodents, non-human primates, etc.), and with different gene combinations.
There are time-dependent neuropathological changes (neuroinflammatory amplification and cytoplasmic inclusions).

Uch-L1 / Park5	Mutations in this gene often result in autosomal dominant PD.
Pink1 / Park6	Pink1 is the first and only protein among many PD-related genes that links mitochondrial dysfunction to the pathogenesis of PD.
DJ-1 / Park7	The pathogenic mechanism may be that the mutation leads to a decrease in the level of Dj-1 protein, which attenuates the body's oxygen radical scavenging function and ultimately increases oxidant damage to neuronal cells.
Lrrk2 / Park8	Mutations in the Lrrk2 gene cause an increase in the kinase activity of its protein and apoptosis, which exerts a toxic effect leading to the development of PD. More than 100 Lrrk2 mutations have been identified in PD patients, and about 20 mutation sites are associated with PD. Moreover, different mutation sites are located in different structural domains with significant regional and ethnic variability.
Atp13a2 / Park9	There is a diversity of mutations in this gene, which directly or indirectly affect the transmembrane structural domains, which in turn leads to the degradation of lysosomes and the formation of toxic aggregates, inducing degeneration of the substantia nigra and the development of PD.
Gigyf2 / Park11	Mutations in this gene have been studied, but the specific function of this protein is not yet fully understood, and further in-depth studies are needed.
Omi / Htra2 / Park13	Htra 2 protein deficiency can lead to impaired apoptosis and cause disease.
Pla2g6 / Park14	Mutations in this gene can result in the Pla2g6 protein weakening or completely losing its mitochondrial protective function. It is therefore unable to repair damage from oxidative stress, which causes neuraxonal degeneration and ultimately PD.
Fbxo7 / Park15	Mutations in Fbxo7 cause dysfunction of its encoded protein Fbxo7. Studies have also reported cranial imaging of associated PD suggesting a large loss of presynaptic dopamine neurons in the substantia nigra striata region.
Gak / Park17	Some studies have found abnormal expression of Gak in the basal ganglia region of PD patients, suggesting a link between this gene and PD.
Hla-Dra / Park18	It has been shown that the Hla-Dra gene contains multiple alleles that increase the risk of developing multiple sclerosis. It has been shown that the rs3129882 locus within the region of the gene, located in intron 1, is most closely associated with PD.

PD is a neurodegenerative disease of uncertain etiology, insidious onset, and slow progression. Alfa Cytology, in addition to the above models, can also provide you with knockouts, conditional knockouts, and live mice that contain these PD-related genes Park2, Park7, Pink1, Lrrk2, Atp13a2, Pla2g6, Fbxo7, and others, depending on the focus of your research. Please feel free to contact us for information on the models you want to help you find a breakthrough from the study of the pathogenic mechanism of these genes.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.